Expression profile of cord blood neutrophils and dysregulation of HSPA1A and OLR1 upon challenge by bacterial peptidoglycan
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摘要Gene expression and network analysis of cord blood neutrophils upon stimulation by peptidoglycan, and induction mechanism of HSPA1A and OLR1 mediated by NFB signals. In newborn infants, the innate cellular system plays a crucial role in the first line of defense against pathogens. Neutrophils are the most abundant leukocytes, and their response to the commonly encountered nosocomial bacterial (Gram positive) infection in newborns remains largely unclear. In this study, a genome-wide expression array analysis was performed on CB neutrophils after challenge by PGN in vitro and compared with neutrophils in CTL cultures without PGN. We investigated responses of neutrophils to PGN and LPS, with respect to cytokine synthesis, chemotaxis, ROS production, cell death, and pathways of HSP response. Our results provide the first comprehensive expressional profile of neonatal neutrophils stimulated by PGN. mRNA levels of 16 up-regulated genes and 6 down-regulated genes were validated by qPCR. Their regulatory networks were identified downstream of TLR-2 and NOD-2, which work in concert toward signals of death, cytoprotection, inflammation, and stress responses. Members of the HSP family were significantly up-regulated in PGN-stimulated neutrophils, compared with those in LPS-stimulated cells. We confirmed protein co-precipitation of HSPA1A and OLR1 in stimulated neutrophils, and their transcription, induced by NF-B but not by MAPK signals. We found increased CD11b, chemotaxis, TNF-, and IL-8 in neutrophils stimulated by PGN or LPS. PGN, but not LPS, increased ROS production. We conclude that neonatal neutrophils are capable of vigorous molecular and functional responses to PGN and suggest that HSP plays a critical role in the host defense mechanism, possibly involving proinflammatory OLR1 and CD11b-facilitated chemotaxis.
著者Fong ON, Chan KYY, Leung KT, Lam HS, Cheung HM, Leung TY, Li KR, Ng PC
期刊名稱Journal of Leukocyte Biology
出版年份2014
月份1
卷號95
期次1
出版社Society for Leukocyte Biology
頁次169 - 178
國際標準期刊號0741-5400
電子國際標準期刊號1938-3673
語言英式英語
關鍵詞differential expression profile, heat shock proteins, human neonate, lipopolysaccharide
Web of Science 學科類別Cell Biology; CELL BIOLOGY; Hematology; HEMATOLOGY; Immunology; IMMUNOLOGY

上次更新時間 2020-19-09 於 01:39