title: Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes.
abstract: BACKGROUND
  CC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes.
  
  
  OBJECTIVE
  To identify the mechanism underlying CCL22 production by HaCaT cells.
  
  
  METHODS
  We investigated the signal transduction pathways by which TNF-α and IFN-γ stimulate HaCaT cells to produce CCL22 by adding various inhibitors.
  
  
  RESULTS
  TNF-α- and IFN-γ-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1.
  
  
  CONCLUSIONS
  Our results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.
authors.affiliation: Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Yano
authors.affiliation: Department of Dermatology, Nippon Medical School, Tokyo, Japan.
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Saeki
authors.affiliation: Department of Dermatology, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Komine
authors.affiliation: Department of Dermatology, Kanto Central Hospital, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kagami
authors.affiliation: Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tsunemi
authors.affiliation: Department of Dermatology, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Mamitaro
authors.initials: M
authors.lastname: Ohtsuki
authors.affiliation: Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Nakagawa
keywords: Chemokine CCL17; Chemokine CCL22; Epidermal growth factor receptor; HaCaT keratinocytes
references.citation: Eur J Cancer. 2014 Jul;50(11):1855-63
references.pmid: 24857781
references.citation: EMBO J. 1999 Oct 15;18(20):5601-8
references.pmid: 10523304
references.citation: Biochem Biophys Res Commun. 2012 Jan 27;417(4):1254-9
references.pmid: 22227193
references.citation: J Dermatol Sci. 1998 Jul;17(3):167-81
references.pmid: 9697045
references.citation: J Invest Dermatol. 2005 Sep;125(3):491-8
references.pmid: 16117790
references.citation: J Investig Allergol Clin Immunol. 2011;21(5):354-62
references.pmid: 21905498
references.citation: Am J Pathol. 2003 Jul;163(1):303-12
references.pmid: 12819035
references.citation: Mol Immunol. 2009 Jun;46(10 ):1925-34
references.pmid: 19371952
references.citation: J Dermatol Sci. 2003 Apr;31(2):111-7
references.pmid: 12670721
references.citation: J Invest Dermatol. 2012 Nov;132(11):2593-600
references.pmid: 22673732
references.citation: Int Immunol. 2002 Jul;14(7):767-73
references.pmid: 12096036
references.citation: Biochem J. 2000 Jul 15;349(Pt 2):427-34
references.pmid: 10880341
references.citation: Exp Cell Res. 2003 Oct 15;290(1):108-19
references.pmid: 14516792
references.citation: Mol Cell Biol. 2002 Aug;22(15):5380-94
references.pmid: 12101233
references.citation: Cell Immunol. 2004 Mar;228(1):27-33
references.pmid: 15203317
references.citation: J Dermatol Sci. 2003 Feb;31(1):37-42
references.pmid: 12615362