Prostaglandin E2 suppresses CCL27 production through EP2 and EP3 receptors in human keratinocytes

Prostaglandin E2–EP3 signaling suppresses skin inflammation in murine contact hypersensitivity

“…These results indicate that multiple signaling pathways might function downstream of EP 3 . It was shown recently that the Ca 21 signaling from EP 3 can inhibit nuclear factor kB activation in keratinocytes, 29 which is consistent with regulation of expression of CXCL1 mRNA by nuclear factor kB activity. 30 The precise molecular mechanisms underlying the anti-inflammatory effect of EP 3 remain to be elucidated.…”

IL-17 suppresses TNF-α–induced CCL27 production through induction of COX-2 in human keratinocytes

“…We recently found that PGE 2 induced cyclic AMP or Ca 21 signals through EP2 or EP3 receptors on keratinocytes, respectively, and both signals suppressed TNF-a-induced NF-kB activity and CCL27 production. 4 When PGE 2 is released from keratinocytes in autocrine and paracrine manners, PGE 2 concentrations on the surface of keratinocytes might be much higher than those of cultured supernatants. Thus endogenously produced PGE 2 might more effectively act on keratinocytes and thus more potently suppress CCL27 production than exogenously added PGE 2 .…”

“…The cDNA was thermocycled for PCR by using primers for CCL27, COX-2, COX-1, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as previously described. 1,4,17 PCR products were analyzed by means of electrophoresis, and densitometric analysis was performed with ATTO lane analyzer version 3 (ATTO Corp, Osaka, Japan). CCL27, COX-1, or COX-2 mRNA levels were normalized to that of GAPDH and are shown as a fold induction.…”

“…18 Transient transfection was performed with Fugene 6 (Roche, Indianapolis, Ind), as previously described. 4 Keratinocytes were plated in 35-mm dishes and grown to about 60% confluence. pNF-kB-luc or pCOX-2-luc and herpes simplex virus thymidine kinase promoter-linked renilla luciferase vector mixed with Fugene 6 were added to keratinocytes.…”

“…We recently found that TNF-a promoted CCL27 production in human keratinocytes at least partially by activating nuclear factor kB (NF-kB) and that the chemical mediator prostaglandin E 2 (PGE 2 ) suppressed TNF-a-induced CCL27 production by inhibiting NF-kB activity. 4 The cytokine IL-17 is released from activated memory T cells. 5 IL-17 production is increased in lesions of patients with asthma, and IL-17 might induce airway neutrophil infiltration by inducing IL-8 production in bronchial epithelial cells or promote airway remodeling by inducing production of the profibrotic cytokines IL-6 and IL-11 in fibroblasts.…”