MKP1 regulates the induction of MCP1 by Streptococcus pneumoniae pneumolysin in human epithelial cells.
Epithelial cells act as the first line of host defense against microbes by producing a range of different molecules for clearance. Chemokines facilitate the clearance of invaders through the recruitment of leukocytes. Thus, upregulation of chemokine expression represents an important innate host defense response against invading microbes such as Streptococcus pneumoniae. In this study, we report that the expression of Monocyte Chemotactic Protein 1 (MCP1) was highly induced in response to S. pneumoniae in vitro and in vivo. Among numerous virulence factors, pneumococcal pneumolysin was found to be the major factor responsible for this induction. Furthermore, MCP1 induction was mediated by the p38 mitogen-activated protein kinase (MAPK) whose activation was controlled by MAPK phosphatase 1 (MKP1). Therefore, this study reveals novel roles of pneumolysin in mediating MKP1 expression for the regulation of MCP1 expression in human epithelial cells.
Shin
Hee-Sung
HS
Department of Biotechnology and Bioinformatics, Korea University, Yeongi, 339-700, Korea.
Yoo
In-Hwa
IH
Kim
Yong-Jae
YJ
Lee
Ji-Yun
JY
Kim
Hyong-Bai
HB
Jin
Shouguang
S
Ha
Un-Hwan
UH
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics; D013290:Streptococcal Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D013301:Streptolysins / Q000378:metabolism; D014774:Virulence; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D034741:RNA, Small Interfering; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1