PMID- 30709353 OWN - NLM STAT- MEDLINE DCOM- 20190226 LR - 20200225 IS - 1746-6148 (Electronic) IS - 1746-6148 (Linking) VI - 15 IP - 1 DP - 2019 Feb 1 TI - All-trans retinoic acid inhibits lipopolysaccharide-induced inflammatory responses in bovine adipocytes via TGFbeta1/Smad3 signaling pathway. PG - 48 LID - 10.1186/s12917-019-1791-2 [doi] LID - 48 AB - BACKGROUND: Dairy cows with metabolic disorder in peripartal period display high inflammatory levels. Adipose tissue is a major endocrine organ, which is closely related to systemic inflammation. Retinoic acid (RA), an active metabolite of vitamin A, has shown potential therapeutic immunomodulatory properties. The objective of the study was to examine the effect of all-trans-RA (ATRA), the biologically most active metabolite of vitamin A, on lipopolysaccharide (LPS)-induced bovine adipocytes inflammatory responses and elucidate the underlying mechanisms. Primary cultured bovine adipocytes were treated with ATRA in the presence or absence of LPS. The treated cells were examined for the inflammatory responses and the activity of transforming growth factor beta 1 (TGFbeta1) /Smad3 signaling pathway. RESULTS: LPS treatment significantly decreased the expression levels of TGFbeta1/Smad3 components and increased the content of pro-inflammatory cytokines. Treatment with ATRA could over-activate TGFbeta1/Smad3 signaling pathway in bovine adipocytes and reversed the over-production of pro-inflammatory cytokines and inhibition of anti-inflammatory cytokines induced by LPS. Importantly, inhibition of TGFbeta1/Smad3 signaling diminished the effects of ATRA on suppressing the proinflammatory responses induced by LPS. Furthermore, activation of TGFbeta1/Smad3 signaling further extended the effects of ATRA on suppressing the proinflammatory responses on LPS stimulation. CONCLUSION: In conclusion, ATRA stimulates TGFbeta1/Smad3 signaling pathway and further suppresses bovine adipocytes inflammatory responses induced by LPS. FAU - Xu, Qiushi AU - Xu Q AD - Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. FAU - Jia, Hongdou AU - Jia H AD - Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. FAU - Ma, Li AU - Ma L AD - Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. FAU - Liu, Guowen AU - Liu G AD - Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. FAU - Xu, Chuang AU - Xu C AD - College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China. FAU - Li, Ying AU - Li Y AD - Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. FAU - Li, Xinwei AU - Li X AUID- ORCID: 0000-0002-0765-677X AD - Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. lixinwei100@126.com. FAU - Li, Xiaobing AU - Li X AD - Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China. xbli@jlu.edu.cn. LA - eng GR - 31572581/National Natural Science Foundation of China/ GR - 31472247/National Natural Science Foundation of China (CN)/ GR - 31402265/National Natural Science Foundation of China (CN)/ GR - 31772810/National Natural Science Foundation of China (CN)/ GR - 20170101148JC/Natural Science Foundation of Jilin Province (CN)/ PT - Journal Article DEP - 20190201 PL - England TA - BMC Vet Res JT - BMC veterinary research JID - 101249759 RN - 0 (Interleukin-17) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Smad3 Protein) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 5688UTC01R (Tretinoin) SB - IM MH - Adipocytes/*drug effects/metabolism/physiology MH - Animals MH - Cattle MH - Cells, Cultured MH - Inflammation/*drug therapy/metabolism/physiopathology MH - Interleukin-17/metabolism MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides/pharmacology MH - Real-Time Polymerase Chain Reaction MH - Signal Transduction/*drug effects MH - Smad3 Protein/*metabolism MH - Transforming Growth Factor beta1/*metabolism MH - Tretinoin/*pharmacology MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC6359792 OTO - NOTNLM OT - All-trans retinoic acid OT - Bovine adipocytes OT - Inflammatory responses OT - TGFbeta1/Smad3 signaling COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The Ethics Committee on the Use and Care of Animals at Jilin University approved the study protocol (Changchun, China). The study was approved by the farm owner and signed a Consent Form. All animals used in this study were handled in accordance with the Guiding Principles of Animal Experiments by the Chinese Society of Laboratory Animal Sciences [2015 clinical trial (2015-121)]. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/02/03 06:00 MHDA- 2019/02/27 06:00 PMCR- 2019/02/01 CRDT- 2019/02/03 06:00 PHST- 2018/08/16 00:00 [received] PHST- 2019/01/21 00:00 [accepted] PHST- 2019/02/03 06:00 [entrez] PHST- 2019/02/03 06:00 [pubmed] PHST- 2019/02/27 06:00 [medline] PHST- 2019/02/01 00:00 [pmc-release] AID - 10.1186/s12917-019-1791-2 [pii] AID - 1791 [pii] AID - 10.1186/s12917-019-1791-2 [doi] PST - epublish SO - BMC Vet Res. 2019 Feb 1;15(1):48. doi: 10.1186/s12917-019-1791-2.