HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts Via P38 MAPK and NF-κB Signaling Pathways

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2013 Dec 5

PMID 24302816

Citations 38

Authors

Zheng-Wen He

Yang-Hua Qin

Zhi-Wei Wang

Yan Chen

Qian Shen

Sheng-Ming Dai

Affiliations

Soon will be listed here.

Abstract

Synovial fibroblasts (SF) play a central role in the inflammatory and destructive process in rheumatoid arthritis (RA). High-mobility group box chromosomal protein 1 (HMGB1) or lipopolysaccharide (LPS) alone failed to induce significant changes in proliferation of cultured SF from RA patients, but premixed HMGB1 with LPS (HMGB1-LPS) significantly facilitated SF proliferation. HMGB1 alone failed to induce IL-6, MMP-3, and MMP-13 production in cultured SF but greatly enhanced LPS-induced expression of IL-6, MMP-3, and MMP-13 at both mRNA and protein levels. HMGB1-LPS synergistically upregulated TLR4 and receptor for advanced glycation endproducts (RAGE) expression on the surface of SF. Both blockers of TLR4 and RAGE significantly inhibited the synergistic effects of HMGB1-LPS on the production of IL-6 and MMPs, but blocking antibodies to TLR2 failed. HMGB1-LPS synergistically increased intracellular levels of phosphorylated p38 and phosphorylated I κ B. Furthermore, both NF- κ B inhibitor Bay11-7085 and p38 inhibitor SB203580 significantly suppressed the enhanced production of IL-6 and MMPs induced by HMGB1-LPS. In conclusion, HMGB1 acts in synergy with LPS to upregulate TLR4 and RAGE expression on the surface of SF in RA and then to augment IL-6, MMP-3, and MMP-13 production, which depends on p38 MAPK and NF-κB activation.

Citing Articles

The Role of Alarmins in the Pathogenesis of Rheumatoid Arthritis, Osteoarthritis, and Psoriasis.

Kielbowski K, Stanska W, Bakinowska E, Rusinski M, Pawlik A Curr Issues Mol Biol. 2024; 46(4):3640-3675.

PMID: 38666958 PMC: 11049642. DOI: 10.3390/cimb46040228.

Establishment and comparison of human term placenta-derived trophoblast cells†.

Vidal Jr M, Radnaa E, Vora N, Khanipov K, Antich C, Ferrer M Biol Reprod. 2024; 110(5):950-970.

PMID: 38330185 PMC: 11484515. DOI: 10.1093/biolre/ioae026.

Demonstration of ameliorating effect of papaverine in sepsis-induced acute lung injury on rat model through radiology and histology.

Ozkul B, Sever I, Yigitturk G, Elgormus C, Gur S, Erbas O Ulus Travma Acil Cerrahi Derg. 2023; 29(9):963-971.

PMID: 37681716 PMC: 10560817. DOI: 10.14744/tjtes.2023.73580.

The mechanism of action of paeoniae radix rubra-angelicae sinensis radix drug pair in the treatment of rheumatoid arthritis through PI3K/AKT/NF-κB signaling pathway.

Li J, Zhang X, Guo D, Shi Y, Zhang S, Yang R Front Pharmacol. 2023; 14:1113810.

PMID: 36992829 PMC: 10040578. DOI: 10.3389/fphar.2023.1113810.

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection.

Wang Y, Wang L, Hu F, Zou M, Luo R, Sun Y Cells. 2022; 11(18).

PMID: 36139393 PMC: 9496866. DOI: 10.3390/cells11182817.

References

Ivanov S, Dragoi A, Wang X, Dallacosta C, Louten J, Musco G . A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood. 2007; 110(6):1970-81. PMC: 1976374. DOI: 10.1182/blood-2006-09-044776. View

Hamada T, Torikai M, Kuwazuru A, Tanaka M, Horai N, Fukuda T . Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum. 2008; 58(9):2675-85. DOI: 10.1002/art.23729. View

Hreggvidsdottir H, Ostberg T, Wahamaa H, Schierbeck H, Aveberger A, Klevenvall L . The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J Leukoc Biol. 2009; 86(3):655-62. DOI: 10.1189/jlb.0908548. View

Merenmies J, Pihlaskari R, Laitinen J, WARTIOVAARA J, Rauvala H . 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. J Biol Chem. 1991; 266(25):16722-9. View

Loeser R, Yammani R, Carlson C, Chen H, Cole A, Im H . Articular chondrocytes express the receptor for advanced glycation end products: Potential role in osteoarthritis. Arthritis Rheum. 2005; 52(8):2376-85. PMC: 1488730. DOI: 10.1002/art.21199. View

Miyazawa K, Mori A, Yamamoto K, Okudaira H . Transcriptional roles of CCAAT/enhancer binding protein-beta, nuclear factor-kappaB, and C-promoter binding factor 1 in interleukin (IL)-1beta-induced IL-6 synthesis by human rheumatoid fibroblast-like synoviocytes. J Biol Chem. 1998; 273(13):7620-7. DOI: 10.1074/jbc.273.13.7620. View

Noss E, Brenner M . The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis. Immunol Rev. 2008; 223:252-70. DOI: 10.1111/j.1600-065X.2008.00648.x. View

Arnett F, Edworthy S, Bloch D, McShane D, Fries J, Cooper N . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3):315-24. DOI: 10.1002/art.1780310302. View

Sims G, Rowe D, Rietdijk S, Herbst R, Coyle A . HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010; 28:367-88. DOI: 10.1146/annurev.immunol.021908.132603. View

10.

Zurolo E, Iyer A, Maroso M, Carbonell C, Anink J, Ravizza T . Activation of Toll-like receptor, RAGE and HMGB1 signalling in malformations of cortical development. Brain. 2011; 134(Pt 4):1015-32. DOI: 10.1093/brain/awr032. View

11.

Bartok B, Firestein G . Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010; 233(1):233-55. PMC: 2913689. DOI: 10.1111/j.0105-2896.2009.00859.x. View

12.

Wahamaa H, Schierbeck H, Hreggvidsdottir H, Palmblad K, Aveberger A, Andersson U . High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts. Arthritis Res Ther. 2011; 13(4):R136. PMC: 3239379. DOI: 10.1186/ar3450. View

13.

Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M . High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum. 2003; 48(4):971-81. DOI: 10.1002/art.10859. View

14.

Garcia-Arnandis I, Guillen M, Castejon M, Gomar F, Alcaraz M . Haem oxygenase-1 down-regulates high mobility group box 1 and matrix metalloproteinases in osteoarthritic synoviocytes. Rheumatology (Oxford). 2010; 49(5):854-61. DOI: 10.1093/rheumatology/kep463. View

15.

Ostberg T, Wahamaa H, Palmblad K, Ito N, Stridh P, Shoshan M . Oxaliplatin retains HMGB1 intranuclearly and ameliorates collagen type II-induced arthritis. Arthritis Res Ther. 2008; 10(1):R1. PMC: 2374449. DOI: 10.1186/ar2347. View

16.

Schierbeck H, Lundback P, Palmblad K, Klevenvall L, Erlandsson-Harris H, Andersson U . Monoclonal anti-HMGB1 (high mobility group box chromosomal protein 1) antibody protection in two experimental arthritis models. Mol Med. 2011; 17(9-10):1039-44. PMC: 3188862. DOI: 10.2119/molmed.2010.00264. View

17.

Neumann E, Lefevre S, Zimmermann B, Gay S, Muller-Ladner U . Rheumatoid arthritis progression mediated by activated synovial fibroblasts. Trends Mol Med. 2010; 16(10):458-68. DOI: 10.1016/j.molmed.2010.07.004. View

18.

Vincenti M, Coon C, Brinckerhoff C . Nuclear factor kappaB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1beta-stimulated synovial fibroblasts. Arthritis Rheum. 1998; 41(11):1987-94. DOI: 10.1002/1529-0131(199811)41:11<1987::AID-ART14>3.0.CO;2-8. View

19.

Suzuki M, Tetsuka T, Yoshida S, Watanabe N, Kobayashi M, Matsui N . The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-alpha- or IL-1beta-stimulated rheumatoid synovial fibroblasts. FEBS Lett. 2000; 465(1):23-7. DOI: 10.1016/s0014-5793(99)01717-2. View

20.

Steenvoorden M, Toes R, Ronday H, Huizinga T, Degroot J . RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro. Clin Exp Rheumatol. 2007; 25(5):740-2. View