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((Short description|Small cytokines or signaling proteins secreted by cells))
((Pfam_box 
| Symbol = IL8 
| Name = Small cytokines (intecrine/chemokine), interleukin-8 like 
| image = IL8 Solution Structure.rsh.png
| width = 
| caption = Solution structure of [[interleukin-8]], a chemokine of the CXC subfamily
| Pfam= PF00048
| InterPro= IPR001811
| SMART= 
| Prosite = PDOC00434
| SCOP = 3il8
| TCDB = 
| OPM family= 
| OPM protein= 
| PDB= 
((PDB3|1dok))A:24-90     ((PDB3|1dol)) :24-90     ((PDB3|1don))A:24-90     
((PDB3|1mca))B:29-90     ((PDB3|1ml0))D:24-90     ((PDB3|1dom))B:24-90     
((PDB3|1bo0)) :24-90     ((PDB3|1ncv))B:24-90     ((PDB3|1esr))A:24-90     
((PDB3|1eot)) :24-88     ((PDB3|2eot)) :24-88     ((PDB3|1eih))A:27-89     
((PDB3|1eig))A:27-89     ((PDB3|1je4))A:24-89     ((PDB3|1hun))A:24-89     
((PDB3|1hum))A:24-89     ((PDB3|1b53))B:24-88     ((PDB3|1b50))B:24-88     
((PDB3|1eqt))B:26-88     ((PDB3|1rto))B:24-88     ((PDB3|1u4r))D:24-88     
((PDB3|1hrj))B:24-88     ((PDB3|1u4p))B:24-88     ((PDB3|1b3a))B:25-88     
((PDB3|1rtn))A:24-88     ((PDB3|1u4l))A:24-88     ((PDB3|1u4m))A:24-88     
((PDB3|1g91))A:45-109    ((PDB3|2hcc)) :48-108    ((PDB3|1zxt))A:26-91     
((PDB3|1vmp))A:26-89     ((PDB3|1cm9))B:26-89     ((PDB3|1hfg))A:26-89     
((PDB3|1hfn))A:26-89     ((PDB3|1hhv))A:26-89     ((PDB3|1hff))A:26-33     
((PDB3|1g2s))A:24-88     ((PDB3|1g2t))A:24-88     ((PDB3|1j8i))A:23-84     
((PDB3|1j9o))A:23-84     ((PDB3|1el0))A:24-88     ((PDB3|1nr4))A:24-88     
((PDB3|1nr2))A:24-88     ((PDB3|1f2l))B:26-89     ((PDB3|1b2t))A:26-89     
((PDB3|1m8a))A:27-89     ((PDB3|1ha6))A:28-90     ((PDB3|2il8))A:29-93     
((PDB3|1ilp))A:28-93     ((PDB3|1qe6))A:28-93     ((PDB3|1ikm)) :31-93     
((PDB3|3il8)) :32-93     ((PDB3|1ikl)) :31-93     ((PDB3|1icw))B:34-93     
((PDB3|1ilq))B:28-93     ((PDB3|1il8))B:29-93     ((PDB3|1tvx))C:61-121    
((PDB3|1nap))D:59-121    ((PDB3|1f9p))A:54-121    ((PDB3|1mgs))B:35-101    
((PDB3|1msh))A:35-101    ((PDB3|1msg))A:35-101    ((PDB3|1mi2))A:28-94     
((PDB3|1rhp))D:38-98     ((PDB3|1f9s))B:32-98     ((PDB3|1pfm))C:39-98     
((PDB3|1f9r))D:32-98     ((PDB3|1pfn))A:39-98     ((PDB3|1f9q))D:32-98     
((PDB3|1dn3))A:87-98     ((PDB3|1plf))D:21-82     ((PDB3|1rjt))A:22-89     
((PDB3|1o7z))B:22-89     ((PDB3|1o7y))B:22-89     ((PDB3|1o80))A:22-89     
((PDB3|1lv9))A:22-89     ((PDB3|1sdf)) :22-87     ((PDB3|1qg7))B:22-87     
((PDB3|1a15))B:29-85     ((PDB3|2sdf)) :22-87     ((PDB3|1vmc))A:22-87     
)) 
((Refimprove|date=April 2013))
'''Chemokines''' (((etymology|grc|''χῠμείᾱ'' (khumeíā)|alchemy||''κῑ́νησῐς'' (kī́nēsis)|movement))), or chemotactic cytokines, are a family of small [[cytokine]]s or [[Cell signaling|signaling]] [[protein]]s secreted by [[Cell (biology)|cell]]s that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells.<ref name=":0">((Cite journal|date=2011-03-10|title=Chemokines in health and disease|journal=Experimental Cell Research|language=en|volume=317|issue=5|pages=575–589|doi=10.1016/j.yexcr.2011.01.005|issn=0014-4827|pmc=3063402|last1=Raman |first1=Dayanidhi |last2=Sobolik-Delmaire |first2=Tammy |last3=Richmond |first3=Ann |pmid=21223965 ))</ref><ref>((Cite journal|last1=Charo|first1=Israel F.|last2=Ransohoff|first2=Richard M.|date=2006-02-09|title=The Many Roles of Chemokines and Chemokine Receptors in Inflammation|url=https://doi.org/10.1056/NEJMra052723|journal=New England Journal of Medicine|volume=354|issue=6|pages=610–621|doi=10.1056/NEJMra052723|issn=0028-4793|pmid=16467548))</ref> In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.<ref name=":0" /><ref>((Cite journal|last=Davenport|first=R. D.|date=2009|title=An introduction to chemokines and their roles in transfusion medicine|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1423-0410.2008.01127.x|journal=Vox Sanguinis|language=en|volume=96|issue=3|pages=183–198|doi=10.1111/j.1423-0410.2008.01127.x|pmid=19076338 |issn=1423-0410|hdl=2027.42/74808|s2cid=13880196 |hdl-access=free))</ref>

Cytokine proteins are classified as chemokines according to behavior and structural characteristics. In addition to being known for mediating chemotaxis, chemokines are all approximately 8–10 [[kilodalton]]s in mass and have four [[cysteine]] residues in conserved locations that are key to forming their 3-dimensional shape.

These proteins have historically been known under several other names including the ''SIS family of cytokines'', ''SIG family of cytokines'', ''SCY family of cytokines'', ''Platelet factor-4 superfamily'' or ''intercrines''.  Some chemokines are considered pro-[[inflammation|inflammatory]] and can be induced during an immune response to recruit cells of the [[immune system]] to a site of [[infection]], while others are considered [[homeostatic]] and are involved in controlling the migration of cells during normal processes of tissue maintenance or [[developmental biology|development]].  Chemokines are found in all [[vertebrate]]s, some [[virus]]es and some [[bacteria]], but none have been found in other [[invertebrate]]s.

Chemokines have been classified into four main subfamilies: CXC, CC, CX3C and C. All of these proteins exert their biological effects by interacting with [[G protein]]-linked [[transmembrane receptor]]s called [[chemokine receptor]]s, that are selectively found on the surfaces of their target cells.<ref>((cite journal | vauthors = Mélik-Parsadaniantz S, Rostène W | title = Chemokines and neuromodulation | journal = Journal of Neuroimmunology | volume = 198 | issue = 1–2 | pages = 62–8 | date = July 2008 | pmid = 18538863 | doi = 10.1016/j.jneuroim.2008.04.022 | s2cid = 7141579 ))</ref>

== Function ==
[[Image:Chemokine concentration chemotaxis.svg|thumb|right|300px|
Chemokines released by infected or damaged cells form a concentration gradient. Attracted cells move through the gradient towards the higher concentration of chemokine.]]
The major role of chemokines is to act as a chemoattractant to guide the migration of cells.  Cells that are attracted by chemokines follow a signal of increasing chemokine concentration towards the source of the chemokine. Some chemokines control cells of the [[immune system]] during processes of immune surveillance, such as directing [[lymphocyte]]s to the [[lymph node]]s so they can screen for invasion of pathogens by interacting with [[antigen-presenting cell]]s residing in these tissues.  These are known as [[homeostatic]] chemokines and are produced and secreted without any need to stimulate their source cells.  Some chemokines have roles in development; they promote [[angiogenesis]] (the growth of new [[blood vessel]]s), or guide cells to tissues that provide specific signals critical for cellular maturation. Other chemokines are [[inflammation|inflammatory]] and are released from a wide variety of cells in response to [[bacteria]]l infection, [[virus]]es and agents that cause physical damage such as [[silica]] or the [[Uric acid|urate crystal]]s that occur in [[gout]]. Their release is often stimulated by pro-inflammatory cytokines such as [[interleukin 1]].  Inflammatory chemokines function mainly as chemoattractants for [[leukocyte]]s, recruiting [[monocyte]]s, [[neutrophil]]s and other effector cells from the [[blood]] to sites of [[infection]] or tissue damage. Certain inflammatory chemokines activate cells to initiate an immune response or promote [[wound healing]]. They are released by many different cell types and serve to guide cells of both [[innate immune system]] and [[adaptive immune system]].

==Types by function==
Chemokines are functionally divided into two groups:<ref name="Zlotnik_2011">((cite journal | vauthors = Zlotnik A, Burkhardt AM, Homey B | title = Homeostatic chemokine receptors and organ-specific metastasis | journal = Nature Reviews. Immunology | volume = 11 | issue = 9 | pages = 597–606 | date = August 2011 | pmid = 21866172 | doi = 10.1038/nri3049 | s2cid = 34438005 ))</ref>
*'''Homeostatic''': are constitutively produced in certain tissues and are responsible for basal [[leukocyte]] migration. These include: [[CCL14]], [[CCL19]], [[CCL20]], [[CCL21]], [[CCL25]], [[CCL27]], [[CXCL12]] and [[CXCL13]]. This classification is not strict; for example, CCL20 can act also as pro-inflammatory chemokine.<ref name="Zlotnik_2011" />
*'''Inflammatory''': these are formed under pathological conditions (on pro-inflammatory stimuli, such as [[Interleukin 1|IL-1]], [[TNF-alpha]], [[Lipopolysaccharide|LPS]], or [[virus]]es) and actively participate in the inflammatory response attracting immune cells to the site of [[inflammation]]. Examples are: [[CXCL8|CXCL-8]], [[CCL2]], [[CCL3]], [[CCL4]], [[CCL5]], [[CCL11]], [[CXCL10]].<ref name="Zlotnik_2012">((cite journal | vauthors = Zlotnik A, Yoshie O | title = The chemokine superfamily revisited | journal = Immunity | volume = 36 | issue = 5 | pages = 705–16 | date = May 2012 | pmid = 22633458 | pmc = 3396424 | doi = 10.1016/j.immuni.2012.05.008 ))</ref>

== Homing==
((details|Homing (hematopoietic)))

The main function of chemokines is to manage the migration of [[leukocytes]] ([[homing (hematopoietic)|homing]]) in the respective anatomical locations in inflammatory and [[homeostatic]] processes.

'''Basal''': homeostatic chemokines are basal produced in the [[thymus]] and lymphoid tissues. Their homeostatic function in homing is best exemplified by the chemokines CCL19 and CCL21 (expressed within [[lymph nodes]] and on lymphatic endothelial cells) and their receptor CCR7 (expressed on cells destined for homing in cells to these organs). Using these [[ligand]]s is possible routing [[antigen-presenting cells]] (APC) to lymph nodes during the adaptive immune response. Among other homeostatic chemokine [[receptor (biochemistry)|receptor]]s include: CCR9, CCR10, and CXCR5, which are important as part of the cell addresses for tissue-specific homing of [[leukocytes]]. CCR9 supports the migration of leukocytes into the [[intestine]], CCR10 to the [[skin]] and CXCR5 supports the migration of [[B-cell]] to follicles of [[lymph nodes]]. As well CXCL12 (SDF-1) constitutively produced in the [[bone marrow]] promotes proliferation of progenitor B cells in the bone marrow microenvironment.<ref name="pmid16212895">((cite journal | vauthors = Le Y, Zhou Y, Iribarren P, Wang J | title = Chemokines and chemokine receptors: their manifold roles in homeostasis and disease | journal = Cellular & Molecular Immunology | volume = 1 | issue = 2 | pages = 95–104 | date = April 2004 | pmid = 16212895 | url = http://www.cmi.ustc.edu.cn/1/2/95.pdf ))</ref><ref name="pmid23125030">((cite journal | vauthors = Graham GJ, Locati M | title = Regulation of the immune and inflammatory responses by the 'atypical' chemokine receptor D6 | journal = The Journal of Pathology | volume = 229 | issue = 2 | pages = 168–75 | date = January 2013 | pmid = 23125030 | doi = 10.1002/path.4123 | s2cid = 10825790 ))</ref>

'''Inflammatory''': [[inflammation|inflammatory]] chemokines are produced in high concentrations during [[infection]] or injury and determine the migration of inflammatory leukocytes into the damaged area. Typical inflammatory chemokines include: CCL2, CCL3 and [[CCL5]], CXCL1, CXCL2 and [[CXCL8]]. A typical example is CXCL-8, which acts as a chemoattractant for neutrophils. In contrast to the homeostatic chemokine receptors, there is significant promiscuity (redundancy) associated with binding receptor and  inflammatory chemokines. This often complicates research on receptor-specific therapeutics in this area.<ref name="pmid23125030" />

==Types by cell attracted==

*'''[[Monocyte]]s / [[macrophage]]s''': the key chemokines that attract these cells to the site of inflammation include: CCL2, CCL3, CCL5, CCL7, CCL8, CCL13, CCL17 and [[CCL22]].
*'''[[T-lymphocyte]]s''': the four key chemokines that are involved in the recruitment of T lymphocytes to the site of inflammation are: CCL2, CCL1, CCL22 and CCL17. Furthermore, CXCR3 expression by T-cells is induced following [[T-cell activation]] and activated T-cells are attracted to sites of inflammation where the IFN-y inducible chemokines CXCL9, CXCL10 and CXCL11 are secreted.<ref name="pmid12773510">((cite journal | vauthors = Xie JH, Nomura N, Lu M, Chen SL, Koch GE, Weng Y, Rosa R, Di Salvo J, Mudgett J, Peterson LB, Wicker LS, DeMartino JA | s2cid = 8175160 | title = Antibody-mediated blockade of the CXCR3 chemokine receptor results in diminished recruitment of T helper 1 cells into sites of inflammation | journal = Journal of Leukocyte Biology | volume = 73 | issue = 6 | pages = 771–80 | date = June 2003 | pmid = 12773510 | doi = 10.1189/jlb.1102573 | doi-access =  ))</ref>
*'''[[Mast cell]]s''': on their surface express several receptors for chemokines: CCR1, CCR2, CCR3, CCR4, CCR5, CXCR2, and CXCR4. [[Ligand]]s of these receptors CCL2 and CCL5 play an important role in mast cell recruitment and activation in the [[lung]]. There is also evidence that [[CXCL8]] might be inhibitory of mast cells.
*'''[[Eosinophil]]s''': the migration of eosinophils into various tissues involved several chemokines of CC family: CCL11, CCL24, CCL26, CCL5, CCL7, CCL13, and CCL3. Chemokines [[CCL11]] (eotaxin) and [[CCL5]] (RANTES) acts through a specific receptor [[CCR3 (gene)|CCR3]] on the surface of eosinophils, and eotaxin plays an essential role in the initial recruitment of eosinophils into the lesion.
*'''[[Neutrophil]]s''': are regulated primarily by CXC chemokines. An example CXCL8 (IL-8) is chemoattractant for neutrophils and also activating their metabolic and [[degranulation]].<ref name="pmid12789214">((cite journal | vauthors = Ono SJ, Nakamura T, Miyazaki D, Ohbayashi M, Dawson M, Toda M | title = Chemokines: roles in leukocyte development, trafficking, and effector function | journal = The Journal of Allergy and Clinical Immunology | volume = 111 | issue = 6 | pages = 1185–99; quiz 1200 | date = June 2003 | pmid = 12789214 | doi = 10.1067/mai.2003.1594 | doi-access = free ))</ref>

==Structural characteristics==
[[Image:ChtxChemkinStr2.png|300px|right|thumb|All chemokines share a typical ''[[Beta sheet#Greek key motif|Greek key]]'' structure that is stabilised by [[disulfide bond]]s between conserved [[cysteine]] residues.]]
Proteins are classified into the chemokine family based on their structural characteristics, not just their ability to attract cells. All chemokines are small, with a [[molecular mass]] of between 8 and 10 [[kDa]]. They are approximately 20-50% identical to each other; that is, they share [[gene]] [[Primary structure|sequence]] and [[amino acid]] [[Primary structure|sequence]] homology. They all also possess conserved [[amino acid]]s that are important for creating their 3-dimensional or [[tertiary structure]], such as (in most cases) four [[cysteine]]s that interact with each other in pairs to create a [[Beta sheet#Greek key motif|Greek key]] shape that is a characteristic of chemokines. Intramolecular [[disulfide bond]]s typically join the first to third, and the second to fourth cysteine residues, numbered as they appear in the protein sequence of the chemokine.  Typical chemokine proteins are produced as [[Protein precursor|pro-peptides]], beginning with a signal peptide of approximately 20 amino acids that gets cleaved from the active (mature) portion of the molecule during the process of its secretion from the cell.  The first two cysteines, in a chemokine, are situated close together near the [[N-terminal end]] of the mature protein, with the third cysteine residing in the centre of the molecule and the fourth close to the [[C-terminal end]].  A loop of approximately ten amino acids follows the first two cysteines and is known as the ''N-loop''.   This is followed by a single-turn helix, called a [[3 10 helix|3<sub>10</sub>-helix]], three [[beta strand|β-strands]] and a C-terminal [[Alpha helix|α-helix]].  These helices and strands are connected by turns called ''30s'', ''40s'' and ''50s'' loops; the third and fourth cysteines are located in the 30s and 50s loops.<ref>((cite journal | vauthors = Fernandez EJ, Lolis E | title = Structure, function, and inhibition of chemokines | journal = Annual Review of Pharmacology and Toxicology | volume = 42 | pages = 469–99 | year = 2002 | pmid = 11807180 | doi = 10.1146/annurev.pharmtox.42.091901.115838 ))</ref>
((clear))

==Types by structure==
{| class="wikitable" style="float:right; margin: 10px; width: 355px; font-size: xx-small;"
|-
| colspan="5" style="text-align: center;" | [[Image:ChtxChemokineStruct.png|300px|The four chemokine subfamilies]]
|-
! colspan="5" style="color: blue; background: #ccccff;" | CC chemokines 
|- style="color: black; background: #ccccff;"
! Name !! Gene !! Other name(s) !! Receptor !! Uniprot 
|-
| [[CCL1]] || Scya1 || I-309, TCA-3 || [[CCR8]] || 
|-
| [[CCL2]] || Scya2 || MCP-1 || [[CCR2]] || P13500
|-
| [[CCL3]] || Scya3 || MIP-1a || [[CCR1]] || P10147
|-
| [[CCL4]] || Scya4 || MIP-1β || [[CCR1]], [[CCR5]] || P13236
|-
| [[CCL5]] || Scya5 || RANTES || [[CCR5]] || P13501
|-
| [[CCL6]] || Scya6 || C10, MRP-2 || [[CCR1]] || P27784
|-
| [[CCL7]] || Scya7 || MARC, MCP-3 || [[CCR2]] || P80098
|-
| [[CCL8]] || Scya8 || MCP-2 || [[CCR1]], [[CCR2]], [[CCR5]] || P80075
|-
| [[CCL9]]/[[CCL10]] || Scya9 || MRP-2, CCF18, MIP-1? || [[CCR1]] || P51670
|-
| [[CCL11]] || Scya11 || Eotaxin || [[CCR2]], [[CCR3 (gene)|CCR3]], [[CCR5]] || P51671
|-
| [[CCL12]] || Scya12 || MCP-5 || || Q62401
|-
| [[CCL13]] || Scya13 || MCP-4, NCC-1, Ckβ10 || [[CCR2]], [[CCR3 (gene)|CCR3]], [[CCR5]] || Q99616
|-
| [[CCL14]] || Scya14 || HCC-1, MCIF, Ckβ1, NCC-2, CCL || [[CCR1]] || Q16627
|-
| [[CCL15]] || Scya15 || Leukotactin-1, MIP-5, HCC-2, NCC-3 || [[CCR1]], [[CCR3 (gene)|CCR3]] || Q16663
|-
| [[CCL16]] || Scya16 || LEC, NCC-4, LMC, Ckβ12 || [[CCR1]], [[CCR2]], [[CCR5]], [[CCR8]] || O15467
|-
| [[CCL17]] || Scya17 || TARC, dendrokine, ABCD-2 || [[CCR4]] || Q92583
|-
| [[CCL18]] || Scya18 || PARC, DC-CK1, AMAC-1, Ckβ7, MIP-4 || || P55774
|-
| [[CCL19]] || Scya19 || ELC, Exodus-3, Ckβ11 || [[CCR7]] || Q99731
|-
| [[CCL20]] || Scya20 || LARC, Exodus-1, Ckβ4 || [[CCR6]] || P78556
|-
| [[CCL21]] || Scya21 || SLC, 6Ckine, Exodus-2, Ckβ9, TCA-4 || [[CCR7]] || O00585
|-
| [[CCL22]] || Scya22 || MDC, DC/β-CK || [[CCR4]] || O00626
|-
| [[CCL23]] || Scya23 || MPIF-1, Ckβ8, MIP-3, MPIF-1 || [[CCR1]] || P55773
|-
| [[CCL24]] || Scya24 || Eotaxin-2, MPIF-2, Ckβ6 || [[CCR3 (gene)|CCR3]] || O00175
|-
| [[CCL25]] || Scya25 || TECK, Ckβ15 || [[CCR9]] || O15444
|-
| [[CCL26]] || Scya26 || Eotaxin-3, MIP-4a, IMAC, TSC-1 || [[CCR3 (gene)|CCR3]] || Q9Y258
|-
| [[CCL27]] || Scya27 || CTACK, ILC, Eskine, PESKY, skinkine || [[CCR10]] || Q9Y4X3
|-
| [[CCL28]] || Scya28 || MEC || [[CCR3 (gene)|CCR3]], [[CCR10]] || Q9NRJ3
|-
! colspan="5" style="color: blue; background: #ccccff;" | CXC chemokines 
|- style="color: black; background: #ccccff;" 
! Name !! Gene !! Other name(s) !! Receptor !! Uniprot
|-
| [[CXCL1]] || Scyb1 || Gro-a, GRO1, NAP-3, KC || [[CXCR2]] || P09341
|-
| [[CXCL2]] || Scyb2 || Gro-β, GRO2, MIP-2a || [[CXCR2]] || P19875
|-
| [[CXCL3]] || Scyb3 || Gro-?, GRO3, MIP-2β || [[CXCR2]] || P19876
|-
| [[CXCL4]] || Scyb4 || PF-4 || [[CXCR3B]] || P02776
|-
| [[CXCL5]] || Scyb5 || ENA-78 || [[CXCR2]] || P42830
|-
| [[CXCL6]] || Scyb6 || GCP-2 || [[CXCR1]], [[CXCR2]] || P80162
|-
| [[CXCL7]] || Scyb7 || NAP-2, CTAPIII, β-Ta, PEP || || P02775
|-
| [[interleukin 8|CXCL8]] || Scyb8 || IL-8, NAP-1, MDNCF, GCP-1 || [[CXCR1]], [[CXCR2]] || P10145
|-
| [[CXCL9]] || Scyb9 || MIG, CRG-10 || [[CXCR3]] || Q07325
|-
| [[CXCL10]] || Scyb10 || IP-10, CRG-2 || [[CXCR3]] || P02778
|-
| [[CXCL11]] || Scyb11 || I-TAC, β-R1, IP-9 || [[CXCR3]], [[CXCR7]] || O14625
|-
| [[CXCL12]] || Scyb12 || SDF-1, PBSF || [[CXCR4]], [[CXCR7]] || P48061
|-
| [[CXCL13]] || Scyb13 || BCA-1, BLC || [[CXCR5]] || O43927
|-
| [[CXCL14]] || Scyb14 || BRAK, bolekine || || O95715
|-
| [[CXCL15]] || Scyb15 || Lungkine, WECHE || || Q9WVL7
|-
| [[CXCL16]] || Scyb16 || SRPSOX || [[CXCR6]] || Q9H2A7
|-
| [[CXCL17]] || VCC-1 || DMC, VCC-1 || || Q6UXB2
|-
! colspan="5" style="color: blue; background: #ccccff;" | C chemokines
|- style="color: black; background: #ccccff;" 
! Name !! Gene !! Other name(s) !! Receptor !! Uniprot
|-
| [[XCL1]] || Scyc1 || Lymphotactin a, SCM-1a, ATAC || [[XCR1]] || P47992
|-
| [[XCL2]] || Scyc2 || Lymphotactin β, SCM-1β || [[XCR1]] || Q9UBD3
|-
! colspan="5" style="color: blue; background: #ccccff;" | CX3C chemokines 
|- style="color: black; background: #ccccff;"
! Name !! Gene !! Other name(s) !! Receptor !! Uniprot
|-
| [[CX3CL1]] || Scyd1 || Fractalkine, Neurotactin, ABCD-3 || [[CX3CR1]] || P78423
|}

Members of the chemokine family are divided into four groups depending on the spacing of their first two cysteine residues. Thus the nomenclature for chemokines is, e.g.: CCL1 for the ligand 1 of the CC-family of chemokines, and CCR1 for its respective receptor.

===CC chemokines===
The CC chemokine (or '''β-chemokine''') proteins have two adjacent cysteines ([[amino acids]]), near their [[amino terminus]]. 
There have been at least 27 distinct members of this subgroup reported for mammals, called CC chemokine [[Ligand (biochemistry)|ligands]] ([[#CC chemokines|CCL]])-1 to -28; CCL10 is the same as [[CCL9]]. Chemokines of this subfamily usually contain four cysteines (C4-CC chemokines), but a small number of CC chemokines possess six cysteines (C6-CC chemokines). C6-CC chemokines include CCL1, CCL15, CCL21, CCL23 and CCL28.<ref>((cite journal | vauthors = Laing KJ, Secombes CJ | title = Chemokines | journal = Developmental and Comparative Immunology | volume = 28 | issue = 5 | pages = 443–60 | date = May 2004 | pmid = 15062643 | doi = 10.1016/j.dci.2003.09.006 ))</ref> CC chemokines induce the migration of [[monocyte]]s and other cell types such as [[NK cells]] and [[dendritic cells]].

Examples of CC chemokine include [[CCL2|monocyte chemoattractant protein-1]] (MCP-1 or CCL2) which induces monocytes to leave the bloodstream and enter the surrounding tissue to become tissue [[macrophage]]s.

CCL5 (or [[RANTES]]) attracts cells such as T cells, eosinophils and [[basophil]]s that express the receptor [[CC chemokine receptors#CCR5|CCR5]].

Increased [[CCL11]] levels in blood plasma are associated with [[aging]] (and reduced [[neurogenesis]]) in mice and humans.<ref name="pmid21886162">((cite journal | vauthors = Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T | title = The ageing systemic milieu negatively regulates neurogenesis and cognitive function | journal = Nature | volume = 477 | issue = 7362 | pages = 90–4 | date = August 2011 | pmid = 21886162 | pmc = 3170097 | doi = 10.1038/nature10357 | bibcode = 2011Natur.477...90V ))</ref>

===CXC chemokines===
The two N-terminal cysteines of CXC chemokines (or '''α-chemokines''') are separated by one amino acid, represented in this name with an "X". There have been 17 different CXC chemokines described in mammals, that are subdivided into two categories, those with a specific amino acid sequence (or motif) of [[glutamic acid]]-[[leucine]]-[[arginine]] (or ELR for short) immediately before the first cysteine of the CXC motif (ELR-positive), and those without an ELR motif (ELR-negative). ELR-positive CXC chemokines specifically induce the migration of [[neutrophil]]s, and interact with chemokine receptors [[CXC chemokine receptors#CXCR1 and CXCR2|CXCR1 and CXCR2]]. An example of an ELR-positive CXC chemokine is [[interleukin-8]] (IL-8), which induces neutrophils to leave the bloodstream and enter into the surrounding tissue. Other CXC chemokines that lack the ELR motif, such as [[CXCL13]], tend to be chemoattractant for lymphocytes. CXC chemokines bind to [[CXC chemokine receptors]], of which seven have been discovered to date, designated CXCR1-7.

===C chemokines===
The third group of chemokines is known as the C chemokines (or γ chemokines), and is unlike all other chemokines in that it has only two cysteines; one N-terminal cysteine and one cysteine downstream. Two chemokines have been described for this subgroup and are called XCL1 ([[lymphotactin]]-α) and XCL2 ([[lymphotactin]]-β).

===CX<sub>3</sub>C chemokines===
A fourth group has also been discovered and members have three amino acids between the two cysteines and is termed CX<sub>3</sub>C chemokine (or d-chemokines). The only CX<sub>3</sub>C chemokine discovered to date is called [[fractalkine]] (or CX<sub>3</sub>CL1). It is both secreted and tethered to the surface of the cell that expresses it, thereby serving as both a chemoattractant and as an [[adhesion molecule]].

==Receptors==
((details|Chemokine receptor))

[[Chemokine receptor]]s are [[G protein-coupled receptor]]s containing 7 [[transmembrane helix|transmembrane domain]]s that are found on the surface of [[leukocyte]]s. Approximately 19 different chemokine receptors have been characterized to date, which are divided into four families depending on the type of chemokine they bind; [[CXC chemokine receptors|CXCR]] that bind CXC chemokines, [[CC chemokine receptors|CCR]] that bind CC chemokines, [[CX3CR1]] that binds the sole CX3C chemokine (CX3CL1), and [[XCR1]] that binds the two XC chemokines (XCL1 and XCL2).  They share many structural features; they are similar in size (with about 350 [[amino acid]]s), have a short, acidic N-terminal end, seven helical transmembrane domains with three [[intracellular]] and three [[extracellular]] [[hydrophilic]] loops, and an intracellular C-terminus containing [[serine]] and [[threonine]] residues important for receptor regulation. The first two extracellular loops of chemokine receptors each has a conserved [[cysteine]] residue that allow formation of a disulfide bridge between these loops.  G proteins are coupled to the C-terminal end of the chemokine receptor to allow intracellular signaling after receptor activation, while the N-terminal domain of the chemokine receptor determines ligand binding specificity.<ref name="JASH">((cite journal | vauthors = Murdoch C, Finn A | title = Chemokine receptors and their role in inflammation and infectious diseases | journal = Blood | volume = 95 | issue = 10 | pages = 3032–43 | date = May 2000 | pmid = 10807766 | url = http://bloodjournal.hematologylibrary.org/cgi/pmidlookup?view=long&pmid=10807766 | archive-url = https://archive.today/20130704021711/http://bloodjournal.hematologylibrary.org/cgi/pmidlookup?view=long&pmid=10807766 | url-status = dead | archive-date = 2013-07-04 | doi = 10.1182/blood.V95.10.3032.010k17_3032_3043 ))</ref>

===Signal transduction===
Chemokine receptors associate with G-proteins to transmit [[Cell signaling|cell signals]] following ligand binding. Activation of G proteins, by chemokine receptors, causes the subsequent activation of an [[enzyme]] known as [[phospholipase C]] (PLC). PLC cleaves a molecule called [[phosphatidylinositol (4,5)-bisphosphate]] (PIP2) into two [[second messenger]] molecules known as [[Inositol triphosphate]] (IP3) and [[diglyceride|diacylglycerol]] (DAG) that trigger intracellular signaling events; DAG activates another enzyme called [[protein kinase C]] (PKC), and IP3 triggers the release of [[Calcium in biology|calcium]] from intracellular stores. These events promote many signaling cascades (such as the [[MAPK/ERK pathway|MAP kinase pathway]]) that generate responses like [[chemotaxis]], [[degranulation]], release of [[superoxide]] anions and changes in the avidity of [[cell adhesion molecule]]s called [[integrin]]s within the cell harbouring the chemokine receptor.<ref name="JASH"/>

==Infection control==
The discovery that the β chemokines [[RANTES]], MIP ([[macrophage inflammatory protein]]s) 1α and 1β (now known as CCL5, CCL3 and CCL4 respectively) suppress [[HIV]]-1 provided the initial connection and indicated that these molecules might control infection as part of immune responses in vivo,<ref>((cite journal | vauthors = Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P | title = Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells | journal = Science | volume = 270 | issue = 5243 | pages = 1811–1815 | date = December 1995 | pmid = 8525373 | doi = 10.1126/science.270.5243.1811 | bibcode = 1995Sci...270.1811C | s2cid = 84062618 | url = https://zenodo.org/record/1231052 ))</ref> and that sustained delivery of such inhibitors have the capacity of long-term infection control.<ref name= "Small molecule inhibitor review">((cite journal | vauthors = von Recum HA, Pokorski JK | title = Peptide and protein-based inhibitors of HIV-1 co-receptors | journal = Experimental Biology and Medicine | volume = 238 | issue = 5 | pages = 442–449 | date = May 2013 | pmid = 23856897 | pmc = 3908444 | doi = 10.1177/1535370213480696 ))</ref> The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in [[HIV]] infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection.<ref>((cite journal | vauthors = Garzino-Demo A, Moss RB, Margolick JB, Cleghorn F, Sill A, Blattner WA, Cocchi F, Carlo DJ, DeVico AL, Gallo RC | title = Spontaneous and antigen-induced production of HIV-inhibitory beta-chemokines are associated with AIDS-free status | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 21 | pages = 11986–11991 | date = October 1999 | pmid = 10518563 | pmc = 18399 | doi = 10.1073/pnas.96.21.11986 | bibcode = 1999PNAS...9611986G | jstor = 48922 | doi-access = free ))</ref>

== See also ==
* [[Paracrine signalling]]

== References ==
((Reflist|32em))

== External links ==
* [https://web.archive.org/web/20060901183008/http://cytokine.medic.kumamoto-u.ac.jp/CFC/CK/Chemokine.html The cytokine family database – Chemokines] at kumamoto-u.ac.jp
* [https://web.archive.org/web/20060718014629/http://www.rndsystems.com/chemokine_nomenclature.aspx  The correct chemokine nomenclature] at rndsystems.com

((Cytokines))
((Chemokine receptor modulators))

[[Category:Cytokines]]
[[Category:Signal transduction]]

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