HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR- Signalling Pathway

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2019 Nov 28

PMID 31772499

Citations 21

Authors

Min Zhao

Yao-Yao Bian

Li-Li Yang

Yan-Qi Chen

Ya-Jie Wang

Yan-Ting Ma

Yu-Qiong Pei

Wen-Lin Li

Li Zeng

Affiliations

Soon will be listed here.

Abstract

Intraperitoneal adhesion is a common complication after abdominal surgery, which seriously affects the quality of life of patients. HuoXueTongFu Formula (HXTF) plays an important role in the prevention and treatment of intraperitoneal adhesions. However, the molecular-related mechanisms are still not fully known. In this study, the model of Intrapetitoneal adhesion was established by cecum abrasion and treated with HXTF for one week. RAW264.7 cells were given LPS, IFN-, IL-4, HXTF-medicated serum, and PPAR- agonist/antagonist, respectively. Histopathology, flow cytometry, ELISA, real-time PCR, and Western blotting were used to further detect the related protein, M1/M2 polarization tendency, and PPAR- nuclear translocation. The deposition of collagen fibres reduced in the local area of rats after the operation with HXTF treatment. Similar to IL-4, HXTF induced a tendency for macrophages to polarize toward M2 and promoted peroxisome proliferator-activated receptor-gamma (PPAR-) nuclear translocation. Furthermore, the use of HXTF and PPAR- agonists downregulated macrophage M1 polarization-related factors IL-1, IL-6, and TNF-alpha and upregulated M2 polarization-related factors IL-4, IL-10, and TGF-beta 1. Meanwhile, the use of HXTF and PPAR- agonists downregulated the SOCS3/JAK2/STAT1 pathway and activated the SOCS1/STAT6/PPAR- pathway. These results show that HXTF may reduce intraperitoneal adhesion by inducing macrophage M2 polarization and regulating the SOCS/JAK2/STAT/PPAR- pathway.

Citing Articles

Herbal Formula with anti-inflammatory and fibrinolytic activity regulation for the prevention of postoperative peritoneal adhesions.

Yang L, Wang Y, Li Z, Li W, Chen Y, Kong Z Front Immunol. 2025; 15:1510766.

PMID: 39916958 PMC: 11798944. DOI: 10.3389/fimmu.2024.1510766.

IFN-γ reprograms cardiac microvascular endothelial cells to mediate doxorubicin transport and influences the sensitivity of mice to doxorubicin-induced cardiotoxicity.

Ji H, Ma W, Liu X, Chen H, Liu Y, Ren Z Exp Mol Med. 2025; 57(1):249-263.

PMID: 39843977 PMC: 11799190. DOI: 10.1038/s12276-024-01389-7.

Gene Therapy for Inflammatory Cascade in Intrauterine Injury with Engineered Extracellular Vesicles Hybrid Snail Mucus-enhanced Adhesive Hydrogels.

Peng X, Wang T, Dai B, Zhu Y, Ji M, Yang P Adv Sci (Weinh). 2024; 12(1):e2410769.

PMID: 39454114 PMC: 11714243. DOI: 10.1002/advs.202410769.

Schistosome egg-derived extracellular vesicles deliver Sja-miR-71a inhibits host macrophage and neutrophil extracellular traps via targeting Sema4D.

Liao Y, Zhu Z, Liu Y, Wu J, Li D, Li Z Cell Commun Signal. 2023; 21(1):366.

PMID: 38129877 PMC: 10734185. DOI: 10.1186/s12964-023-01395-8.

Study on the Alleviating Effect and Potential Mechanism of Ethanolic Extract of (L.) Hill. on Lipopolysaccharide-Induced Inflammatory Responses in Macrophages.

Yang Z, Man J, Liu Y, Zhang H, Wu D, Shao D Int J Mol Sci. 2023; 24(22).

PMID: 38003461 PMC: 10671607. DOI: 10.3390/ijms242216272.

References

Whyte C, Bishop E, Ruckerl D, Gaspar-Pereira S, Barker R, Allen J . Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function. J Leukoc Biol. 2011; 90(5):845-54. DOI: 10.1189/jlb.1110644. View

Kersten S, Desvergne B, Wahli W . Roles of PPARs in health and disease. Nature. 2000; 405(6785):421-4. DOI: 10.1038/35013000. View

Nelson V, Nguyen H, Garcia-Canaveras J, Briggs E, Ho W, DiSpirito J . PPARγ is a nexus controlling alternative activation of macrophages via glutamine metabolism. Genes Dev. 2018; 32(15-16):1035-1044. PMC: 6075146. DOI: 10.1101/gad.312355.118. View

Li A, Liu Y, Zhai L, Wang L, Lin Z, Wang S . Activating Peroxisome Proliferator-Activated Receptors (PPARs): a New Sight for Chrysophanol to Treat Paraquat-Induced Lung Injury. Inflammation. 2016; 39(2):928-37. DOI: 10.1007/s10753-016-0326-2. View

Yu T, Zuo Y, Cai R, Huang X, Wu S, Zhang C . SENP1 regulates IFN-γ-STAT1 signaling through STAT3-SOCS3 negative feedback loop. J Mol Cell Biol. 2016; 9(2):144-153. PMC: 7104919. DOI: 10.1093/jmcb/mjw042. View

Attard J, MacLean A . Adhesive small bowel obstruction: epidemiology, biology and prevention. Can J Surg. 2007; 50(4):291-300. PMC: 2386166. View

Zhu T, Zhang W, Feng S, Yu H . Emodin suppresses LPS-induced inflammation in RAW264.7 cells through a PPARγ-dependent pathway. Int Immunopharmacol. 2016; 34:16-24. DOI: 10.1016/j.intimp.2016.02.014. View

Mirza R, Fang M, Novak M, Urao N, Sui A, Ennis W . Macrophage PPARγ and impaired wound healing in type 2 diabetes. J Pathol. 2015; 236(4):433-44. PMC: 4509817. DOI: 10.1002/path.4548. View

Bouhlel M, Derudas B, Rigamonti E, Dievart R, Brozek J, Haulon S . PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 2007; 6(2):137-43. DOI: 10.1016/j.cmet.2007.06.010. View

10.

Jacobi D, Stanya K, Lee C . Adipose tissue signaling by nuclear receptors in metabolic complications of obesity. Adipocyte. 2012; 1(1):4-12. PMC: 3423221. DOI: 10.4161/adip.19036. View

11.

Zhang Z, Yu L, Hui X, Wu Z, Yin K, Yang H . Hydroxy-safflor yellow A attenuates Aβ₁₋₄₂-induced inflammation by modulating the JAK2/STAT3/NF-κB pathway. Brain Res. 2014; 1563:72-80. DOI: 10.1016/j.brainres.2014.03.036. View

12.

Tang L, Zhang H, Wang C, Li H, Zhang Q, Bai J . M2A and M2C Macrophage Subsets Ameliorate Inflammation and Fibroproliferation in Acute Lung Injury Through Interleukin 10 Pathway. Shock. 2016; 48(1):119-129. DOI: 10.1097/SHK.0000000000000820. View

13.

Harris E, MORGAN R, Rodeheaver G . Analysis of the kinetics of peritoneal adhesion formation in the rat and evaluation of potential antiadhesive agents. Surgery. 1995; 117(6):663-9. DOI: 10.1016/s0039-6060(95)80010-7. View

14.

Hong G, Schwandt T, Stein K, Schneiker B, Kummer M, Heneka M . Effects of macrophage-dependent peroxisome proliferator-activated receptor γ signalling on adhesion formation after abdominal surgery in an experimental model. Br J Surg. 2015; 102(12):1506-16. DOI: 10.1002/bjs.9907. View

15.

Fu Y, Tsauo J, Sun Y, Wang Z, Kim K, Lee S . Developmental endothelial locus-1 prevents development of peritoneal adhesions in mice. Biochem Biophys Res Commun. 2018; 500(3):783-789. DOI: 10.1016/j.bbrc.2018.04.158. View

16.

Szanto A, Balint B, Nagy Z, Barta E, Dezso B, Pap A . STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells. Immunity. 2010; 33(5):699-712. PMC: 3052437. DOI: 10.1016/j.immuni.2010.11.009. View

17.

Cortes J, Perez-G M, Rivas M, Zamorano J . Kaempferol inhibits IL-4-induced STAT6 activation by specifically targeting JAK3. J Immunol. 2007; 179(6):3881-7. DOI: 10.4049/jimmunol.179.6.3881. View

18.

Pismensky S, Kalzhanov Z, Eliseeva M, Kosmas I, Mynbaev O . Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation. BMC Surg. 2011; 11:30. PMC: 3266192. DOI: 10.1186/1471-2482-11-30. View

19.

Cai X, Hu S, Yu B, Cai Y, Yang J, Li F . Transglutaminase-catalyzed preparation of crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen composite membrane for postsurgical peritoneal adhesion prevention. Carbohydr Polym. 2018; 201:201-210. DOI: 10.1016/j.carbpol.2018.08.065. View

20.

Yue Y, Yan S, Li H, Zong Y, Yue J, Zeng L . The role of oral fluvastatin on postoperative peritoneal adhesion formation in an experimental rat model. Acta Chir Belg. 2018; 118(6):372-379. DOI: 10.1080/00015458.2018.1444549. View