Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes
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Background: CC chemokine ligand 17 (CCL17) and CCL22are the functional ligands for CCR4. We previously reportedthat inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellularsignal-related kinase (ERK), inhibited tumor necrosisfactor (TNF)-α- and interferon (IFN)-γ-induced productionof CCL17 by the human keratinocyte cell line,HaCaT. Further, an inhibitor of epidermal growth factor receptor(EGFR) enhanced the CCL17 production by thesekeratinocytes. Objective: To identify the mechanism underlyingCCL22 production by HaCaT cells. Methods: We investigatedthe signal transduction pathways by which TNF-αand IFN-γ stimulate HaCaT cells to produce CCL22 by addingvarious inhibitors. Results: TNF-α- and IFN-γ- inducedCCL22 production was inhibited by PD98059, PD153035,Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitorII, and Janus kinase (JAK) inhibitor 1. Conclusion: Ourresults indicate that CCL22 production in HaCaT cells is dependenton ERK, EGFR, p38 MAPK, JNK, and JAK and ismediated by different signal pathways from those regulatingCCL17 production. Altogether, our previous and present resultssuggest that EGFR activation represses CCL17 but enhancesCCL22 production by these cells.
Abstract
Background: CC chemokine ligand 17 (CCL17) and CCL22are the functional ligands for CCR4. We previously reportedthat inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellularsignal-related kinase (ERK), inhibited tumor necrosisfactor (TNF)-α- and interferon (IFN)-γ-induced productionof CCL17 by the human keratinocyte cell line,HaCaT. Further, an inhibitor of epidermal growth factor receptor(EGFR) enhanced the CCL17 production by thesekeratinocytes. Objective: To identify the mechanism underlyingCCL22 production by HaCaT cells. Methods: We investigatedthe signal transduction pathways by which TNF-αand IFN-γ stimulate HaCaT cells to produce CCL22 by addingvarious inhibitors. Results: TNF-α- and IFN-γ- inducedCCL22 production was inhibited by PD98059, PD153035,Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitorII, and Janus kinase (JAK) inhibitor 1. Conclusion: Ourresults indicate that CCL22 production in HaCaT cells is dependenton ERK, EGFR, p38 MAPK, JNK, and JAK and ismediated by different signal pathways from those regulatingCCL17 production. Altogether, our previous and present resultssuggest that EGFR activation represses CCL17 but enhancesCCL22 production by these cells.
참고문헌 (16)
- Xiao T, "Both IL-4 and IL-13 inhibit the TNF-alpha and IFN-gamma enhanced MDC production in a human keratinocyte cell line, HaCaT cells", J Dermatol Sci, 31, pp.111~117 (2003)
- Kobayashi M, "Roxithromycin downmodulates Th2 chemokine production by keratinocytes and chemokine receptor expression on Th2 cells: its dual inhibitory effects on the ligands and the receptors", Cell Immunol, 228, pp.27~33 (2004)
- Komine M, "Mechanism of thymus- and activation- regulated chemokine (TARC)", CCL17 production and its modulation by roxithromycin, 2005, pp.125, 491~498
- Meephansan J, "Regulation of IL-33 expression by IFN-γ and tumor necrosis factor-α in normal human epidermal keratinocytes", J Invest Dermatol, 132, pp.2593~2600 (2012)
- Horikawa T, "IFN-gamma-inducible expression of thymus and activation-regulated chemokine", CCL17 and macrophage-derived chemokine, Int Immunol, pp.2002, 14[DOI]
- Tsuda T, "Lack of evidence for TARC", CCL17 production by normal human keratinocytes in vitro, 2003, pp.31, 37~42
- Holvoet S, "The inhibition of MAPK pathway is correlated with down-regulation of MMP-9 secretion induced by TNF-alpha in human keratinocytes", Exp Cell Res, 290, pp.108~119 (2003)
- Tomic-Canic M, "Epidermal signal transduction and transcription factor activation in activated keratinocytes", J Dermatol Sci, 17, pp.167~181 (1998)
- Goh KC, "p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons", EMBO J, 18, pp.5601~5608 (1999)
- Nguyen VA, "Interferons activate the p42", 44 mitogen-activated protein kinase and JAK-STAT (Janus kinase-signal transducer and activator transcription factor) signalling pathways in hepatocytes:differential regulation by acute ethanol via a protein kinase C-dependent mechanism, 2000, pp.349, 427~434
- Kwon DJ, "Casuarinin suppresses TARC", CCL17 and MDC, Biochem Biophys Res Commun, pp.2012, 417[DOI]
- Qi XF, "The adenylyl cyclase-cAMP system suppresses TARC", CCL17and MDC, Mol Immunol, pp.2009, 46[DOI]
- Mascia F, "Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation", Am J Pathol, 163, pp.303~312 (2003)
- Iordanov MS, "The UV (Ribotoxic) stress response of human keratinocytes involves the unexpected uncoupling of the Ras-extracellular signal-regulated kinase signaling cascade from the activated epidermal growth factor receptor", Mol Cell Biol, 22, pp.5380~5394 (2002)
- Matsui K, "Percutaneous application of peptidoglycan from Staphylococcus aureus induces infiltration of CCR4＋ cells into mouse skin", J Investig Allergol Clin Immunol, 21, pp.354~362 (2011)
- Paul T, "Cytokine regulation by epidermal growth factor receptor inhibitors and epidermal growth factor receptor inhibitor associated skin toxicity in cancer patients", Eur J Cancer, 50, pp.1855~1863 (2014)