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Abnormal activation of various inflammatory pathways has been observed in astrocytes in brain lesions associated with TSC. Increasing evidence supports the involvement of microRNAs in the regulation of astrocyte\u2010mediated inflammatory response. To study the role of inflammation\u2010related microRNAs in TSC, we employed real\u2010time PCR and<jats:italic>in situ<\/jats:italic>hybridization to characterize the expression of miR21, miR146a, and miR155 in TSC lesions (cortical tubers and subependymal giant cell astrocytomas, SEGAs). We observed an increased expression of miR21, miR146a, and miR155 in TSC tubers compared with control and perituberal brain tissue. Expression was localized in dysmorphic neurons, giant cells, and reactive astrocytes and positively correlated with IL\u20101\u03b2 expression. In addition, cultured human astrocytes and SEGA\u2010derived cell cultures were used to study the regulation of the expression of these miRNAs in response to the proinflammatory cytokine IL\u20101\u03b2 and to evaluate the effects of overexpression or knockdown of miR21, miR146a, and miR155 on inflammatory signaling. IL\u20101\u03b2 stimulation of cultured glial cells strongly induced intracellular miR21, miR146a, and miR155 expression, as well as miR146a extracellular release. IL\u20101\u03b2 signaling was differentially modulated by overexpression of miR155 or miR146a, which resulted in pro\u2010 or anti\u2010inflammatory effects, respectively. This study provides supportive evidence that inflammation\u2010related microRNAs play a role in TSC. In particular, miR146a and miR155 appear to be key players in the regulation of astrocyte\u2010mediated inflammatory response, with miR146a as most interesting anti\u2010inflammatory therapeutic candidate. 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