TY - JOUR ID - 250332 TI - Human Neutrophil Elastase Induce Interleukin-10 Expression in Peripheral Blood Mononuclear Cells through Protein Kinase C Theta/Delta and Phospholipase Pathways JO - Cell Journal (Yakhteh) JA - CELLJ LA - en SN - 2228-5806 AU - Kawata, Jin AU - Yamaguchi, Rui AU - Yamamoto, Takatoshi AU - Ishimaru, Yasuji AU - Sakamoto, Arisa AU - Aoki, Manabu AU - Kitano, Masafumi AU - Umehashi, Misako AU - Hirose, Eiji AU - Yamaguchi, Yasuo AD - Y1 - 2016 PY - 2016 VL - 17 IS - 4 SP - 692 EP - 700 KW - Interleukin KW - 10 KW - PBMC KW - Protein kinase C DO - 10.22074/cellj.2016.3841 N2 - ObjectiveNeutrophils have an important role in the rapid innate immune response, and the release or active secretion of elastase from neutrophils is linked to various inflammatory responses. Purpose of this study was to determine how the human neutrophil elastase affects the interleukin-10 (IL-10) response in peripheral blood mononuclear cells (PBMC). Materials and MethodsIn this prospective study, changes in IL-10 messenger RNA (mRNA) and protein expression levels in monocytes derived from human PBMCs were investigated after stimulation with human neutrophil elastase (HNE). A set of inhibitors was used for examining the pathways for IL-10 production induced by HNE. ResultsReverse transcription polymerase chain reaction (RT-PCR) showed that stimulation with HNE upregulated IL-10 mRNA expression by monocytes, while the enzyme-linked immunosorbent assay (ELISA) revealed an increase of IL-10 protein level in the culture medium. A phospholipase C inhibitor (U73122) partially blunt- ed the induction of IL-10 mRNA expression by HNE, while IL-10 mRNA expression was significantly reduced by a protein kinase C (PKC) inhibitor (Rottlerin). A calcium chelator (3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester: TMB-8) inhibited the response of IL-10 mRNA to stimulation by HNE. In addition, pretreatment with a broad-spectrum PKC inhibitor (Ro-318425) partly blocked the response to HNE. Finally, an inhibitor of PKC theta/delta abolished the increased level of IL-10 mRNA expression. ConclusionThese results indicate that HNE mainly upregulates IL-10 mRNA ex- pression and protein production in moncytes via a novel PKC theta/delta, although partially via the conventional PKC pathway. UR - https://www.celljournal.org/article_250332.html L1 - https://www.celljournal.org/article_250332_1e2a881eeb95b814f05eb44fa3536469.pdf ER -