Apigenin, a Potent Suppressor of Dendritic Cell Maturation and Migration, Protects Against Collagen-induced Arthritis

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2015 Oct 31

PMID 26515512

Citations 27

Authors

Xing Li

Yanping Han

Qingyou Zhou

Hongyu Jie

Yi He

Jiaochan Han

Juan He

Yong Jiang

Erwei Sun

Affiliations

Soon will be listed here.

Abstract

This study aimed to investigate whether apigenin (API) suppresses arthritis development through the modulation of dendritic cell functions. Bone marrow-derived dendritic cells (BMDCs) were stimulated in vitro with lipopolysaccharide (LPS) and treated with API for 24 hrs; DC functions, including phenotype expressions, cytokine secretion, phagocytosis and chemotaxis, were then investigated. The effects of API on collagen-induced arthritis (CIA) were examined in vivo, and purified DCs from the lymph nodes (LNs) of API-treated CIA mice were analysed for phenotypes and subsets. In in vitro, API efficiently restrained the phenotypic and functional maturation of LPS-stimulated BMDCs while maintaining phagocytotic capabilities. Moreover, API inhibited the chemotactic responses of LPS-stimulated BMDCs, which may be related to the depressive effect on chemokine receptor 4 (CXCR4). In in vivo, API treatment delayed the onset and reduced the severity of arthritis in CIA mice, and diminished secretion of pro-inflammatory cytokines in the serum and supernatants from the LN cells of the CIA mice. Similar to the in vitro findings, the API-treated mice exhibited reduced expression of co-stimulatory molecules and major histocompatibility complex II on DCs. Furthermore, API treatment strongly down-regulated the number of Langerhans cells, but not plasmacytoid DCs (pDCs) in LNs, which may be related to the depressive effect of API on the expression of CXCR4 on DCs of peripheral blood. These data provide new insight into the mechanism of action of API on arthritis and indicate that the inhibition of maturation and migration of DCs by API may contribute to its immunosuppressive effects.

Citing Articles

From Tea to Functional Foods: Exploring Bunge for Anti-Rheumatoid Arthritis and Unraveling Its Potential Mechanisms.

Dong X, Wang Z, Fu Y, Tian Y, Xue P, Wang Y Nutrients. 2025; 16(24.

PMID: 39770932 PMC: 11680032. DOI: 10.3390/nu16244311.

Apigenin: A Bioflavonoid with a Promising Role in Disease Prevention and Treatment.

Allemailem K, Almatroudi A, Alharbi H, ALSuhaymi N, Alsugoor M, Aldakheel F Biomedicines. 2024; 12(6).

PMID: 38927560 PMC: 11202028. DOI: 10.3390/biomedicines12061353.

The mechanism of dendritic cell-T cell crosstalk in rheumatoid arthritis.

Wang Z, Zhang J, An F, Zhang J, Meng X, Liu S Arthritis Res Ther. 2023; 25(1):193.

PMID: 37798668 PMC: 10552435. DOI: 10.1186/s13075-023-03159-8.

Comparative Analysis of Apigenin-3 Acetate versus Apigenin and Methyl-Prednisolone in Inhibiting Proliferation and Gene Expression of Th1 Cells in Multiple Sclerosis.

Kasiri N, Ghannadian S, Hosseini R, Ahmadi L, Rahmati M, Ashtari F Cell J. 2023; 25(5):307-316.

PMID: 37300292 PMC: 10257058. DOI: 10.22074/cellj.2023.1971743.1154.

EPCR deficiency ameliorates inflammatory arthritis in mice by suppressing the activation and migration of T cells and dendritic cells.

Xue M, Lin H, Liang H, Bereza-Malcolm L, Lynch T, Sinnathurai P Rheumatology (Oxford). 2023; 63(2):571-580.

PMID: 37228024 PMC: 10834933. DOI: 10.1093/rheumatology/kead230.

References

Thomas R, Davis L, Lipsky P . Rheumatoid synovium is enriched in mature antigen-presenting dendritic cells. J Immunol. 1994; 152(5):2613-23. View

Mounho B, Thrall B . The extracellular signal-regulated kinase pathway contributes to mitogenic and antiapoptotic effects of peroxisome proliferators in vitro. Toxicol Appl Pharmacol. 1999; 159(2):125-33. DOI: 10.1006/taap.1999.8740. View

Firestein G . Evolving concepts of rheumatoid arthritis. Nature. 2003; 423(6937):356-61. DOI: 10.1038/nature01661. View

Lee J, Zhou H, Cho S, Kim Y, Lee Y, Jeong C . Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2 expression, adhesion of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules. Arch Pharm Res. 2007; 30(10):1318-27. DOI: 10.1007/BF02980273. View

Yen J, Khayrullina T, Ganea D . PGE2-induced metalloproteinase-9 is essential for dendritic cell migration. Blood. 2007; 111(1):260-70. PMC: 2200811. DOI: 10.1182/blood-2007-05-090613. View

Burska A, Boissinot M, Ponchel F . Cytokines as biomarkers in rheumatoid arthritis. Mediators Inflamm. 2014; 2014:545493. PMC: 3964841. DOI: 10.1155/2014/545493. View

Seo H, Choi H, Kim S, Choi Y, Woo S, Shin I . Apigenin induces apoptosis via extrinsic pathway, inducing p53 and inhibiting STAT3 and NFκB signaling in HER2-overexpressing breast cancer cells. Mol Cell Biochem. 2012; 366(1-2):319-34. DOI: 10.1007/s11010-012-1310-2. View

Brand D, Latham K, Rosloniec E . Collagen-induced arthritis. Nat Protoc. 2007; 2(5):1269-75. DOI: 10.1038/nprot.2007.173. View

Steinman R . Dendritic cells and immune-based therapies. Exp Hematol. 1996; 24(8):859-62. View

10.

Myers L, Rosloniec E, Cremer M, Kang A . Collagen-induced arthritis, an animal model of autoimmunity. Life Sci. 1997; 61(19):1861-78. DOI: 10.1016/s0024-3205(97)00480-3. View

11.

Johnson L, Clasper S, Holt A, Lalor P, Baban D, Jackson D . An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium. J Exp Med. 2006; 203(12):2763-77. PMC: 2118156. DOI: 10.1084/jem.20051759. View

12.

Leung B, Conacher M, Hunter D, McInnes I, Liew F, Brewer J . A novel dendritic cell-induced model of erosive inflammatory arthritis: distinct roles for dendritic cells in T cell activation and induction of local inflammation. J Immunol. 2002; 169(12):7071-7. DOI: 10.4049/jimmunol.169.12.7071. View

13.

Weyand C . New insights into the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2000; 39 Suppl 1:3-8. DOI: 10.1093/oxfordjournals.rheumatology.a031491. View

14.

Banchereau J, Steinman R . Dendritic cells and the control of immunity. Nature. 1998; 392(6673):245-52. DOI: 10.1038/32588. View

15.

Walsh N, Crotti T, Goldring S, Gravallese E . Rheumatic diseases: the effects of inflammation on bone. Immunol Rev. 2005; 208:228-51. DOI: 10.1111/j.0105-2896.2005.00338.x. View

16.

Ratzinger G, Stoitzner P, Ebner S, Lutz M, Layton G, Rainer C . Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin. J Immunol. 2002; 168(9):4361-71. DOI: 10.4049/jimmunol.168.9.4361. View

17.

Huang R, Yu Y, Cheng W, OuYang C, Fu E, Chu C . Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol. 2010; 184(12):6815-21. DOI: 10.4049/jimmunol.0903991. View

18.

Wang L, Kuang L, Hitron J, Son Y, Wang X, Budhraja A . Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression. Toxicol Appl Pharmacol. 2013; 272(1):108-16. PMC: 3823051. DOI: 10.1016/j.taap.2013.05.028. View

19.

Wenink M, Han W, Toes R, Radstake T . Dendritic cells and their potential implication in pathology and treatment of rheumatoid arthritis. Handb Exp Pharmacol. 2008; (188):81-98. DOI: 10.1007/978-3-540-71029-5_4. View

20.

Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S . Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992; 176(6):1693-702. PMC: 2119469. DOI: 10.1084/jem.176.6.1693. View