Journal of Inflammation Research (Dec 2021)
Qing-Luo-Yin Alleviated Experimental Arthritis in Rats by Disrupting Immune Feedback Between Inflammatory T Cells and Monocytes: Key Evidences from Its Effects on Immune Cell Phenotypes
Abstract
Dan-Dan Wang,1,2,* Xin-Yue Wu,3,* Ji-Yang Dong,3 Xiu-Ping Cheng,1,2 Shao-Fei Gu,1,2 Opeyemi Joshua Olatunji,4 Yan Li,1,2 Jian Zuo1,5,6 1Xin’an Medicine Research Center, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Republic of China; 2Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 3Department of Electronic Science, Xiamen University, Xiamen, 361005, People’s Republic of China; 4Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, 90110, Thailand; 5Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 6Anhui Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wuhu, 241000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Li; Jian Zuo Email [email protected]; [email protected]: Qing-Luo-Yin (QLY) is an anti-rheumatic herbal formula. Despite the well-investigated therapeutic efficacy of QLY, its immune regulatory properties are largely unknown. CD4+ T cells and monocytes are two key parameters in rheumatoid arthritis (RA). This study investigated the changes in these cells in QLY-treated RA animal models.Materials and Methods: RA models were induced in male SD rats and were orally treated with QLY. Dynamic metabolic changes in collagen-induced arthritis (CIA) rats were monitored by 1H NMR approach. The immunity profiles of CIA and adjuvant-induced arthritis (AIA) rats were evaluated using immunohistochemical, PCR, ELISA, cytokine chip, flow cytometry, and immunofluorescence experiments. The bioactive components in QLY were identified by bioinformatic-guided LC-MS analyses. The compounds with high abundance in QLY decoction and easily absorbed were taken as key anti-rheumatic components and used to treat blood-derived immune cells using in vitro experiments.Results: The results indicated that QLY decreased Th17 cells frequency and T cells-released IL-6, IL-17 and GM-CSF in CIA rats, which was attributed to the impaired lymphocyte maturation and altered differentiation. QLY inhibited lactic acid production and inflammatory polarization in the monocytes during the peak period of AIA and CIA. AIA monocytes elicited significant increase in Th17 cells counts, IL-6 and IL-1β secretion in co-cultured splenocytes, which was abrogated by QLY. QLY-containing serum suppressed the phosphorylation of JNK and p65 in AIA lymphocyte-stimulated normal monocytes and consequently inhibited iNOS and IL-1β expression as well as IL-6 and IL-1β production. Matrine, sinomenine and sophocarpine were identified as major bioactive compounds in QLY. These identified compounds effectively inhibited the development of inflammatory T cells using concentrations detected in QLY-treated rats. At higher concentrations (20-fold increase), the chemical stimuli significantly suppressed the production of IL-1β in AIA monocytes by inhibiting JNK and p65 pathways.Conclusion: By targeting inflammatory T cells and monocytes as well as disrupting their interplay, QLY improved immune environment in RA models especially during the active stages of disease.Keywords: traditional Chinese medicine, rheumatoid arthritis, innate immunity, T cells, chronic inflammation, metabolomics
