Disease relevance of CCL20

• In addition, we characterized human melanoma cells as a novel CCL20 source and as cathepsin producers [1].
• By immunohistochemistry, we show that CXCL12 and, to a lesser extent, CCL20 are expressed by reactive astrocytes in multiple sclerosis lesions [2].
• Selective early production of CCL20, or macrophage inflammatory protein 3alpha, by human mast cells in response to Pseudomonas aeruginosa [3].
• In humans, immunostaining of LARC/CCL20 was weak if any in normal skin tissues but strongly augmented in lesional skin tissues with atopic dermatitis [4].
• In addition, the authors' results suggest that CCL20 is used by CCR6 regulatory T cells in the complex process of controlling colitis because transcripts for this chemokine were expressed to a higher level in protected animals [5].

High impact information on CCL20

• The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by beta-defensin [6].
• A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells [7].
• IL-21-treated cell culture supernatants enhanced in vitro lymphocyte migration, and this effect was inhibited by anti-MIP-3alpha antibody [7].
• A subset of genes involved in inflammation and related to the nuclear factor kappaB pathway was coregulated with CCL20 . Among these genes, the antiapoptotic factor TNFAIP3 was highly expressed in the FAE [8].
• CCL23 , which was not coregulated in vitro with CCL20 , was also specifically expressed in the FAE [8].

Chemical compound and disease context of CCL20

• We found that TNF-alpha and E. coli LPS enhanced the production of CCL20 by HGF treated with IL-1beta [9].
• Increased expression of MIP-3alpha/CCL20 in peripheral blood mononuclear cells from patients with ulcerative colitis and its down-regulation by sulfasalazine and glucocorticoid treatment [10].

Biological context of CCL20

• We report that MIP-3alpha/CCL20-induced calcium flux and chemotaxis can be enhanced significantly on peripheral blood and tonsillar B cells after activation by cross-linking surface Ag receptors [11].
• Of particular interest is the fact that the enhanced activity on B cells was not associated with an increase in CCR6 expression as assessed by levels of receptor mRNA, surface staining, or MIP-3alpha/CCL20 binding sites, or by a change in the affinity of the receptor for ligand [11].
• In this review, the discovery, the gene and protein structure, the in vitro biological activities, the cell and inducer specific expression and the tissue distribution of CCL20 and CCR6 are discussed [12].
• Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA-positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non-polarized [13].
• RESULTS: Significant up-regulation for CCL20/CCR6 was detected in both cancer types [14].

Anatomical context of CCL20

• CCL20-expressing keratinocytes colocalize with skin-infiltrating T cells in lesional psoriatic skin [15].
• CCL20, like human beta-defensin (hBD)-2, is a potent chemoattractant for CCR6-positive immature dendritic cells and T cells in addition to recently found antimicrobial activities [16].
• In vitro, CCL20 attracted skin-homing CLA+ T cells of both normal and psoriatic donors; however, psoriatic lymphocytes responded to lower concentrations of chemokine and showed higher chemotactic responses [15].
• CCL20 production was up-regulated by IL-1alpha and TNF-alpha in all cell lines tested, and in human metastatic melanoma cells [1].
• Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter [17].

Associations of CCL20 with chemical compounds

• Reverse transcription-PCR and Western blot analysis demonstrated that the human mast cells (HMC-1) express CCL20 mRNA and are able to produce a significant amount (32.4 ng/ml) of CCL20 protein following stimulation by calcium ionophore and phorbol myristate acetate [3].
• Interestingly, the CCL20 response of mast cells to P. aeruginosa was relatively resistant to inhibition by the corticosteroid dexamethasone, interleukin-10, or cyclosporine, while GM-CSF production was potently inhibited [3].
• However, P. aeruginosa-induced CCL20 production was blocked by the protein kinase C (PKC) inhibitor Ro 31-8220 and a PKC pseudosubstrate [3].
• These results indicate that the growth of a proportion of human HCC cells may be mediated by CCL20-CCR6 axis, like HuH7 cells, in an autocrine or paracrine manner [18].
• Tumor necrosis factor-alpha, CXC chemokine ligand 8 (CXCL8), CCL2, and C chemokine ligand 20 (CCL20) release was enhanced in response to all PAMPs tested, in a time- and dose-dependent manner [19].
• The hypoxic synovial microenvironment may directly contribute to the persistent inflammation associated with JIA by increasing CCL20 production by SF monocytic cells, thus representing a potential therapeutic target [20].

Regulatory relationships of CCL20

• LARC induced migration in 293/EBNA-1 cells stably expressing GPR-CY4 with a bi-modal dose-response curve [21].
• In this study, we examined the human mast cell production of both CCL20 and granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine for innate immune responses in the lung, in response to Pseudomonas aeruginosa [3].
• CCL20 chemokine induces both osteoblast proliferation and osteoclast differentiation: Increased levels of CCL20 are expressed in subchondral bone tissue of rheumatoid arthritis patients [22].
• We thus designated this chemokine as LARC from Liver and Activation-Regulated Chemokine [23].
• Lymphotoxin beta (LTalpha1beta2) expressed on the membrane of immune cells triggers CCL20 expression in enterocytes [8].

Other interactions of CCL20

• Taken together, these findings strongly suggest that CCL20/CCR6 may play a role in the recruitment of T cells to lesional psoriatic skin [15].
• It is concluded that in addition to its role in homeostatic trafficking of leukocytes, LARC/MIP-3alpha can function as an inflammatory chemokine during host defense [24].
• Similar results were obtained if gp120-treated cells were triggered by CCL21 and CCL20 [25].
• IL-1beta, TNF-alpha, CCL20 were also up-regulated from six-fold to 30-fold in TcOB preparations from decayed teeth [26].
• Significant CCL20 production did not occur following immunoglobulin E-mediated activation of CBMC under conditions which induced a substantial GM-CSF response [3].

Analytical, diagnostic and therapeutic context of CCL20

• In mice, intradermal injection of IL-1alpha and TNF-alpha rapidly induced a local accumulation of transcripts for LARC/CCL20 and its receptor CCR6 with a lag of several hours in the latter [4].
• Furthermore, we could demonstrate that CRC patients who developed liver metastases express significantly more CCL20 and CCL21 in the liver in comparison with an unaffected control group [27].
• Total RNA was isolated and the expression of CCL20 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR [28].
• For quantitative considerations, CXCL8, CCL20, interleukin 1, and tumor necrosis factor-alpha (TNF-alpha) levels were determined in SF by ELISA [28].
• Cell culture experiments, however, confirmed the ability of TNF-alpha in SF to induce CCL20 mRNA expression in blood PMN [28].

References