Abstract:
: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 αvβ3 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.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Yang H,Guo H,Fan K,Zhang B,Zhao L,Hou S,Qian W,Zhang D,Wang H,Dai J,Guo Ydoi
10.1016/j.molimm.2011.06.435subject
Has Abstractpub_date
2011-09-01 00:00:00pages
2019-26issue
15-16eissn
0161-5890issn
1872-9142pii
S0161-5890(11)00647-Xjournal_volume
48pub_type
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