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  • Macrophage migration inhibitory factor is required for recruitment of scar-associated macrophages during liver fibrosis.

Macrophage migration inhibitory factor is required for recruitment of scar-associated macrophages during liver fibrosis.

Journal of leukocyte biology (2014-11-16)
Mark A Barnes, Megan R McMullen, Sanjoy Roychowdhury, Nabil Z Madhun, Kathryn Niese, Mitchell A Olman, Abram B Stavitsky, Richard Bucala, Laura E Nagy
ZUSAMMENFASSUNG

Recruitment of peripheral monocytes to the liver is a key contributor to the response to injury. MIF can act as a chemokine and cytokine, regulating innate immune responses in many tissues and cell types. We hypothesized that MIF contributes to the progression of CCl4-induced hepatic fibrosis by regulating recruitment of SAM. SAMs dynamically regulate HSC activation and ECM degradation. To gain insight into the role of MIF in progression of liver fibrosis, we investigated markers of fibrosis and immune responses after chronic CCl4 administration to female C57BL/6 and MIF(-/-) mice. Chronic CCl4 exposure increased activation of HSC in WT mice, indicated by increased expression of αSMA mRNA and protein, as well as mRNA for collagen 1α1; these responses were blunted in female MIF(-/-) mice. Despite lower activation of HSC in MIF(-/-) mice, accumulation of ECM was similar in WT and MIF(-/-)mice, suggesting a decreased rate of ECM degradation. Recruitment of SAMs was lower in MIF(-/-) mice compared with WT mice, both in their initial inflammatory phenotype, as well as in the later phase as proresolution macrophages. The decreased presence of resolution macrophages was associated with lower expression of MMP13 in MIF(-/-) mice. Taken together, these data indicate that MIF-dependent recruitment of SAMs contributes to degradation of ECM via MMP13, highlighting the importance of appropriate recruitment and phenotypic profile of macrophages in the resolution of fibrosis.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
Tetrachlorkohlenstoff, reagent grade, 99.9%
Sigma-Aldrich
Monoklonaler Anti-Aktin-Antikörper , α-Glattmuskel, clone 1A4, ascites fluid
Supelco
Tetrachlorkohlenstoff, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Tetrachlorkohlenstoff, anhydrous, ≥99.5%
Supelco
Tetrachlorkohlenstoff, analytical standard
Sigma-Aldrich
Anti-Cytochrom P450-Enzym-CYP2E1-Antikörper, serum, Chemicon®