PMID- 31300043 OWN - NLM STAT- MEDLINE DCOM- 20191209 LR - 20221207 IS - 1297-9716 (Electronic) IS - 0928-4249 (Print) IS - 0928-4249 (Linking) VI - 50 IP - 1 DP - 2019 Jul 12 TI - Matrine inhibits IL-1beta secretion in primary porcine alveolar macrophages through the MyD88/NF-kappaB pathway and NLRP3 inflammasome. PG - 53 LID - 10.1186/s13567-019-0671-x [doi] LID - 53 AB - Our previous studies demonstrated that matrine directly acts on the replication process of porcine reproductive and respiratory syndrome virus (PRRSV). Matrine inhibits viral replication and is also associated with the NF-kappaB signalling pathway. These results suggest that matrine has antiviral and anti-inflammatory effects. However, the specific anti-inflammatory mechanism of matrine is still unclear. In this study, we investigated the anti-IL-1beta mechanism of matrine, as IL-1beta is a major inflammatory cytokine, in porcine alveolar macrophages (PAMs) stimulated with 4 mug PRRSV 5'-untranslated region (UTR) RNA and 1 mug/mL LPS. After 5'UTR RNA and LPS co-stimulation of PAMs for 12 h, the expression of IL-1beta, IL-6, IL-8 and TNF-alpha was significantly increased. The results also showed that co-stimulation induced the expression of MyD88, and activated the NF-kappaB signalling pathway and NLRP3 inflammasome. Furthermore, matrine treatment downregulated MyD88, NLRP3 and caspase-1 expression, inhibited ASC speck formation, suppressed IkappaBalpha phosphorylation, and interfered with the translocation of NF-kappaB from the cytoplasm to the nucleus. These results suggest that matrine plays an important role in PAMs co-stimulated with PRRSV 5'UTR RNA and LPS via its effect on NF-kappaB and the NLRP3 inflammasome. These findings lay the foundation for the exploration of the clinical application of matrine in PRRSV disease. FAU - Sun, Panpan AU - Sun P AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China. AD - School of Life Science and Engineering, Foshan University, Foshan, 528000, Guangdong, People's Republic of China. FAU - Sun, Na AU - Sun N AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China. FAU - Yin, Wei AU - Yin W AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China. FAU - Sun, Yaogui AU - Sun Y AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China. FAU - Fan, Kuohai AU - Fan K AD - Laboratory Animal Center, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China. FAU - Guo, Jianhua AU - Guo J AD - Department of Veterinary Pathobiology, Schubot Exotic Bird Health Center, Texas A&M University, College Station, TX, 77843, USA. FAU - Khan, Ajab AU - Khan A AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China. FAU - He, Yongming AU - He Y AD - School of Life Science and Engineering, Foshan University, Foshan, 528000, Guangdong, People's Republic of China. ymhe@fosu.edu.cn. FAU - Li, Hongquan AU - Li H AUID- ORCID: 0000-0002-2030-5587 AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China. livets@163.com. LA - eng GR - 31702285/National Natural Science Foundation of China/ GR - 2017YFD0501500/National Key R&D Program of China/ GR - 2017001/the Scientific Innovation Project of Shanxi Agricultural University/ PT - Journal Article DEP - 20190712 PL - England TA - Vet Res JT - Veterinary research JID - 9309551 RN - 0 (Alkaloids) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Quinolizines) RN - 0 (RNA, Viral) RN - 0 (Matrines) SB - IM MH - Alkaloids/*pharmacology MH - Animals MH - Inflammasomes/*immunology MH - Interleukin-1beta/*metabolism MH - Lipopolysaccharides/pharmacology MH - Macrophages/*drug effects/immunology MH - Myeloid Differentiation Factor 88/immunology MH - NF-kappa B/*immunology MH - NLR Family, Pyrin Domain-Containing 3 Protein/immunology MH - Porcine respiratory and reproductive syndrome virus/physiology MH - Quinolizines/*pharmacology MH - RNA, Viral/genetics MH - Signal Transduction/immunology MH - Sus scrofa MH - Transfection/veterinary MH - Matrines PMC - PMC6626430 COIS- The authors declare that they have no competing interests. EDAT- 2019/07/14 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/07/12 CRDT- 2019/07/14 06:00 PHST- 2019/03/12 00:00 [received] PHST- 2019/06/22 00:00 [accepted] PHST- 2019/07/14 06:00 [entrez] PHST- 2019/07/14 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/07/12 00:00 [pmc-release] AID - 10.1186/s13567-019-0671-x [pii] AID - 671 [pii] AID - 10.1186/s13567-019-0671-x [doi] PST - epublish SO - Vet Res. 2019 Jul 12;50(1):53. doi: 10.1186/s13567-019-0671-x.