Histone Deacetylation 10 Alleviates Inflammation After Intracerebral Hemorrhage via the PTPN22/NLRP3 Pathway in Rats

The NOD-like Receptor family Pyrin domain-containing 3 (NLRP3) inflammasome has a crucial role in the inflammatory process that occurs during intracerebral hemorrhage (ICH)-induced injury. Histone deacetylase 10 (HDAC10) is a newly identified class II histone deacetylase involved in immune responses. However, how HDAC10 affects the inflammatory response after ICH remains unknown. In this study, we investigated whether HDAC10 relieves ICH injury by suppressing NLRP3 inflammasome activation through the protein tyrosine Phosphatase, nonreceptor type 22 (PTPN22) pathway. We induced ICH in Sprague-Dawley rats (healthy, male adult) with a single infusion of autologous blood. To knockdown HDAC10, we injected siRNA into the rats. To further explore the mechanisms underlying the role of HDAC10 in ICH injury, PTPN22 was silenced. HDAC10 levels were upregulated after ICH in humans and rats, and reached peak levels 24 h after ICH induction in rats. HDAC10 silencing aggravated ICH injury, as demonstrated by increased modified neurological severity scores, brain water content, Evans blue extravasation, and number of myeloperoxidase (MPO) cells, and the results of Nissl and H&E staining. Furthermore, HDAC10 knockdown increased the expression of PTPN22 and accentuated inflammatory responses mediated by the NLRP3 inflammasome. HDAC10 silencing increased NLRP3 inflammasome activation, and this was effectively reversed by PTPN22 knockdown using siRNA. Furthermore, HDAC10 silencing also promoted the interaction of PTPN22 and NLRP3. Our study demonstrated that HDAC10 silencing aggravated NLRP3-mediated inflammatory responses after ICH in rats via the PTPN22 pathway. These results suggest that regulating the NLRP3 inflammasome may be a novel method to ameliorate ICH injury.