Cytokine
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Pro-inflammatory cytokines are crucial for fighting infection and establishing immunity. Recently, other proteins, such as danger-associated molecular patterns (DAMPs), have also been appreciated for their role in inflammation and immunity. ⋯ This review examines how various inflammasomes promote the release of IL-1β, IL-18 and HMGB1 to combat pathogenic situations. Each of these effector molecules plays distinct roles during sterile inflammation, responding to viral, bacterial and parasite infection, and tailoring the innate immune response to specific threats.
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Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that was initially identified by its ability to inhibit the movement of macrophages. Cell migration is a highly complex process involving changes to the cytoskeleton and cell adhesion molecules, and is regulated by the Rho GTPases. A simple model using human monocytic U-937 cells to elicit the classic MIF response was implemented to examine the mechanism of MIF-induced migration inhibition. ⋯ Collectively, these data suggest that the MIF-mediated migration inhibition is mediated by the outcome of G-protein signaling, and in less adherent cells such as those of the monocyte/macrophage lineage, RhoA directly affects net translocation through its ability to induce cell body contraction. These findings demonstrate that CXCR4 can mediate MIF signaling in the absence of CD74 in addition to serving as a MIF co-receptor along with CD74. These results correlate MIF activity to specific and sequential Rho GTPase activity perturbations, and given that CXCR4 functions in numerous processes, suggests potential roles for the modulation of cell movement in those events including development, cell survival and viral infection.