Ann Dermatol.  2015 Apr;27(2):152-156. 10.5021/ad.2015.27.2.152.

Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes

Affiliations
  • 1Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
  • 2Department of Dermatology, Nippon Medical School, Tokyo, Japan. h-saeki@nms.ac.jp
  • 3Department of Dermatology, Jichi Medical University, Shimotsuke, Japan.
  • 4Department of Dermatology, Kanto Central Hospital, Tokyo, Japan.
  • 5Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.

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)-alpha- and interferon (IFN)-gamma-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-alpha and IFN-gamma stimulate HaCaT cells to produce CCL22 by adding various inhibitors.
RESULTS
TNF-alpha- and IFN-gamma-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.
CONCLUSION
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.

Keyword

Chemokine CCL22; Chemokine CCL17; Epidermal growth factor receptor; HaCaT keratinocytes

MeSH Terms

Bays
Cell Line
Chemokine CCL17
Chemokine CCL22
Humans
Interferons
JNK Mitogen-Activated Protein Kinases
Keratinocytes*
Ligands
p38 Mitogen-Activated Protein Kinases
Phosphotransferases
Protein Kinases
Receptor, Epidermal Growth Factor
Signal Transduction
Tumor Necrosis Factor-alpha
Chemokine CCL17
Chemokine CCL22
Interferons
JNK Mitogen-Activated Protein Kinases
Ligands
Phosphotransferases
Protein Kinases
Receptor, Epidermal Growth Factor
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases
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