期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 120, 期 2, 页码 366-373出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2007.04.033
关键词
monocyte; adaptation; organic dust; swine; cytokines; inflammation; protein kinase C
资金
- NIEHS NIH HHS [K08 ES015522] Funding Source: Medline
Background: Organic dust exposure results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory diseases. Mechanisms underlying this modulated response are not clear. Objective: This study investigated the effects of repeat versus single organic dust exposure-induced inflammatory mediators and protein kinase C (PKC) activity in monocytes. Methods: Settled organic dust was obtained from swine confinement facilities. Promonocytic THP-1 cells and human peripheral blood monocytes were pretreated with or without dust extract and then restimulated. Culture supernatants were evaluated for TNF-alpha, IL-6, CXCL8, and IL-10. Responses were compared with endotoxin-depleted dust, LPS, and peptidoglycan. PKC isoform (alpha, delta, epsilon, zeta) activation was evaluated by direct kinase activity. PKC isoform inhibitors' effects on TNF-alpha secretion were studied. Results: Single exposure to organic dust stimulated monocyte secretion of TNF-alpha, IL-6, CXCL8, and IL-10 compared with unstimulated cells. TNF-a and IL-6 were diminished in pretreated cells restimulated with dust. Secretion of CXCL8 and IL-10 remained persistently elevated. TNF-alpha responses were retained after marked depletion of endotoxin. Dust exposure induced significant PKC alpha, delta, epsilon, and zeta activation, peaking at 30 to 60 minutes. PKC isoform activation was attenuated in repeat exposed cells. Inhibition of PKC alpha and PKC epsilon reduced dust-induced TNF-alpha secretion. Conclusion: Repeat organic dust exposure modulated inflammatory mediator production in monocytes independent of endotoxin. The inability of PKC to be reactivated may account for this observation. Clinical implications: Targeting PKC and specific mediators associated with repetitive organic dust exposure may result in novel therapeutic strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据