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Publication : Clearance of Propionibacterium acnes by kupffer cells is regulated by osteopontin through modulating the expression of p47phox.

First Author  Yang H Year  2011
Journal  Mol Immunol Volume  48
Issue  15-16 Pages  2019-26
PubMed ID  21737140 Mgi Jnum  J:177212
Mgi Id  MGI:5294499 Doi  10.1016/j.molimm.2011.06.435
Citation  Yang H, et al. (2011) Clearance of Propionibacterium acnes by kupffer cells is regulated by osteopontin through modulating the expression of p47phox. Mol Immunol 48(15-16):2019-26
abstractText  Osteopontin (OPN) is a cytokine with multiple functions, including the regulation of innate immune response. However, the detailed function and mechanism of OPN in host defense against invaded microorganisms remain unclear. In this report, we revealed that OPN could affect the clearance of Propionibacterium acnes in kupffer cells. In a murine model of P. acnes induced hepatic granuloma, OPN-deficient mice or wild-type (WT) mice treated with anti-OPN mAb exhibited more hepatic granuloma formation than WT mice. Increased infiltration of intrahepatic leukocytes, higher expression of TLRs, and significantly upregulated level of proinflammatory cytokines of liver tissue were observed in OPN-deficient mice after P. acnes challenge. Moreover, in vitro assay showed that kupffer cells isolated from OPN(-/-) mice exhibited impairment in clearance of P. acnes. Kupffer cells isolated from OPN(-/-) mice showed reduced level of NADPH oxidase-mediated reactive oxygen species (ROS) in response to P. acnes, which was regulated by NADPH oxidase subunit p47phox. Further investigation revealed that OPN interaction with alphavbeta3 integrin activated PI3K and ERK signal pathways, leading to the expression of p47phox. Taken together, these data demonstrated an important role of OPN in enhancing the antimicrobial innate immune response by modulation of bacterium clearance activity in kupffer cells.
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