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. Author manuscript; available in PMC: 2013 Dec 15.
Published in final edited form as: J Immunol. 2012 Nov 19;189(12):5965–5975. doi: 10.4049/jimmunol.1201437

Figure 8. miR-451 regulates a negative cascade to modulate pro-inflammatory cytokine expression.

Figure 8

(A) miR-451 targets the 3′-UTR of YWHAZ to decrease protein levels. YWHAZ binds ZFP36 to decrease binding to AU-rich elements in the 3′-UTR of the proinflammatory cytokines TNF, IFN-β, and IL-6 and the chemokines CCL3 and CCL5. IL-6 and IFN-β positively regulate miR-451 expression in dendritic cells. (B) Antagomir data supports the following model for the observed increased expression of IL-6, TNF, CCL3, CCL5, and IFN-β in primary dendritic cells treated with miR-451 antagomir. Antagomir treatment increases YWHAZ protein and mRNA levels, which correlates with decreased ZFP36 levels. Increasing YWHAZ expression by transduction resulted in an analogous decrease in ZFP36 and increase in IL-6, TNF, and chemokine expression. Increased IL-6 and IFN-β levels can positively regulate miR-451 expression while miR-451 expression culminates in decreased IL-6 expression, which together serves to buffer IL-6 expression.