Endogenous miR22 is associated with a diverse range of biological processes through post-translational modification of gene expression and its deregulation results in various diseases including cancer. Its expression is usually tissue or cell-specific, however, the reasons behind this tissue or cell specificity are not clearly outlined till-date. Therefore, our keen interest was to investigate the mechanisms of tissue or cell-specific expression of miR22. In the current study, miR22 expression showed a tissues-specific difference in the poly(I:C) induced inflammatory mouse lung and brain tissues. The cell-specific different expression of miR22 was also observed in inflammatory glial cells and endothelial cells. The pattern of RPL29 expression was also similar to miR22 in these tissues and cells under the same treatment. Interestingly, the knockdown of RPL29 exerted an inhibitory effect on miR22 and its known transcription factors including Fos-B and c-Fos. Fos-B and c-Fos were also differentially expressed in the two cell lines transfected with poly(I:C). The knockdown of c-Fos also exerted its negative effects on miR22 expression in both cells. These findings suggest that RPL29 might have regulatory roles on tissue or cell-specific expression of miR22 through the transcription activities of c-Fos and also possibly through Fos-B.