Aim Inducible nitric oxide synthase (iNOS) makes a great contribution to host defense and inflammation.In many settings, lipopolysaccharide (LPS) induces iNOS expression through activation of the inhibitor of κBα (IκBα)nuclear factorκB (NFκB) cascade, whereas interferonγ(IFNγ) acts through Janus kinase (JAK)signal transducer and activator of transcription 1 (STAT1) signals.Heat shock factor 1 (HSF1), a major regulator of heat shock protein transcription, has been shown to regulate the production of proinflammatory cytokines such as tumor necrosis factoroα (TNFα) and interleukin6 (IL6).But it remains obscure whether and how HSF1 affects iNOS induction.Methods Western blot was used to measure the protein expression.The mRNA level was measured by real timePCR.Silence of HSF1 was achieved by small interfering RNA.Nitric oxide (NO) content and NFκB binding activity were assayed by commercial kits.Chromatin immunoprecipitation (ChIP) was used to measure the binding activity of NFκB and STAT1 to iNOS promoters.Results HSF1 inhibition or knockdown prevented the LPSand/or IFNγstimulated iNOS protein expression in cultured microglia.HSF1 inhibition blocked iNOS mRNA transcription.These inhibitory effects of HSF1 inhibition on iNOS expression were confirmed in brain tissues from endotoxemic mice.Further analysis showed that HSF1 inhibition had no effect on IκBα degradation and NFκB or STAT1 phosphorylation in LPS/IFNγstimulated cells.The nuclear transport of active NFκB or STAT1 was also not affected by HSF1 inhibition.But HSF1 inhibition reduced the binding of NFκB and STAT1 to their DNA elements.In addition, HSF1 inhibition reduced NFκB and STAT1 bindings to iNOS promoter inside the LPS/IFNγstimulated cells.Conclusions This preventing effect of HSF1 inhibition on iNOS mRNA transcription presents the necessary role of HSF1 in iNOS induction.