Prostaglandin E₂ induces oncostatin M expression in human chronic wound macrophages through Axl receptor tyrosine kinase pathway.
Prostaglandin E₂ induces oncostatin M expression in human chronic wound macrophages through Axl receptor tyrosine kinase pathway.
复制标题
DOI：
10.4049/jimmunol.1102762
复制
发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Roy S
中科院分区：
文献类型：
--
作者：
Ganesh K;Das A;Dickerson R;Khanna S;Parinandi NL;Gordillo GM;Sen CK;Roy S
单核细胞和巨噬细胞（mangiocytes and macrophages，简称M）是可塑性细胞，其功能受微环境因素的影响。浸泡伤口组织的伤口流体反映了伤口微环境。目前有关伤口炎症的文献主要基于对血液单核细胞源性细胞（MDM）的研究，这些细胞从未暴露于伤口微环境。我们试图配对比较MDM与从患者慢性伤口中分离的MM。抑瘤素M（OSM）在配对伤口组织中差异过表达。PGE_2及其代谢产物13，14-dihydro-15-keto-PGE_2（PGE-M）在创面液中含量丰富，可诱导创面组织发生OSM。一致地，在从植入小鼠伤口中的富含PGE 2的PVA海绵分离的骨髓中观察到OSM mRNA的诱导。用PGE 2或PGE-M处理人THP-1细胞衍生的细胞引起OSM的剂量依赖性诱导。信号转导通路的表征表明EP 4受体和cAMP信号转导参与。在人骨髓中，PGE 2使受体酪氨酸激酶（RTK）Axl磷酸化。cAMP类似物也诱导Axl磷酸化，证明cAMP和RTK途径之间的相互作用。PGE 2依赖性Axl磷酸化导致AP-1反式激活，其直接涉及OSM的诱导型表达。用重组OSM处理人包皮或小鼠切除伤口导致抗炎反应，表现为内毒素诱导的TNFα和IL-1β表达减弱。OSM治疗还改善了愈合早期炎症阶段的伤口闭合。总之，这项工作认识到伤口液中的PGE 2是mNOSM的有效诱导剂，mNOSM是一种在皮肤伤口愈合中具有抗炎作用的细胞因子。
Monocytes and macrophages (mϕ) are plastic cells whose functions are governed by microenvironmental cues. Wound fluid bathing the wound tissue reflects the wound microenvironment. Current literature on wound inflammation is primarily based on the study of blood monocyte-derived mϕ (MDM), cells that have never been exposed to the wound microenvironment. We sought to pair-match compare MDMs with mϕ isolated from chronic wound of patients. Oncostatin M (OSM) was differentially overexpressed in pair-matched wound mϕ. Both PGE2 and its metabolite 13,14-dihydro-15-keto-PGE2 (PGE-M) were abundant in wound fluid and induced OSM in wound-site mϕ. Consistently, induction of OSM mRNA was observed in mϕ isolated from PGE2–enriched PVA sponges implanted in murine wounds. Treatment of human THP-1 cell-derived mϕ with PGE2 or PGE-M caused dose-dependent induction of OSM. Characterization of the signal transduction pathways demonstrated the involvement of EP4 receptor and cAMP signaling. In human mϕ, PGE2 phosphorylated Axl, a receptor tyrosine kinase (RTK). Axl phosphorylation was also induced by a cAMP analog demonstrating interplay between the cAMP and RTK pathways. PGE2–dependent Axl phosphorylation led to AP-1 transactivation which is directly implicated in inducible expression of OSM. Treatment of human mϕ or mice excisional wounds with recombinant OSM resulted in an anti-inflammatory response as manifested by attenuated expression of endotoxin-induced TNFα and IL-1β. OSM treatment also improved wound closure during the early inflammatory phase of healing. In summary this work recognizes PGE2 in the wound-fluid as a potent inducer of mϕ OSM, a cytokine with anti-inflammatory role in cutaneous wound healing.
登录
查看更多内容
影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
Schorpp-Kistner, M
DOI：
10.1161/atvbaha.107.160580
发表时间：
2008-03-01
影响因子：
8.7
作者：
Kastl, Stefan P.;Speidl, Walter S.;Wojta, Johann
通讯作者：
Wojta, Johann
影响因子：
5.3
作者：
Dumas A;Lagarde S;Laflamme C;Pouliot M
通讯作者：
Pouliot M
影响因子：
4.4
作者：
Lucas, Tina;Waisman, Ari;Eming, Sabine A.
通讯作者：
Eming, Sabine A.
影响因子：
5.3
作者：
Albasanz-Puig, Adaia;Murray, Jacqueline;Wijelath, Errol S.
通讯作者：
Wijelath, Errol S.