Skip to main content
Erschienen in: Immunologic Research 1/2018

07.12.2017 | Original Article

Dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus induced septic arthritis correlating alteration in the level of interferon gamma and interleukin-10 in terms of TNFR2 blocking

verfasst von: Sahin Sultana, Rajen Dey, Biswadev Bishayi

Erschienen in: Immunologic Research | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Severity of S. aureus septic arthritis is correlated to prolonged inflammation by inflammatory cytokines like TNF-α, IL-1β, and IL-6 even after successful elimination of bacteria. Role of TNF-α via TNFR2 is not well established in this aspect. IFN-γ induces TNF-α release from the macrophages augmenting the inflammatory arthritis. IL-10 modulates the levels of pro-inflammatory cytokines promoting resolution of inflammation. TNF-α-TNFR2 signaling upregulates both of these cytokines. Higher level of MMP-2 induction by inflammatory cytokines during arthritis promotes tissue destruction. Whether dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus arthritis by modulating local and systemic cytokine milieu mainly due to TNFR-2 blocking was an obvious question. Here, we attempted the effects of neutralization of MMP-2 and TNFR2 on S. aureus arthritis and its impact on pro-inflammatory cytokines and some other parameters related to tissue destruction. Reduction in arthritis index was noticed in infected mice treated with both MMP-2 inhibitor and TNFR2 antibody. Lowest levels of inflammatory cytokines, iNOS, RANKL, NF-κb, JNK kinase, ROS, and MPO, and lysozyme activity were observed in combined neutralization group at 9 and 15 dpi, but at 3 dpi, most of the above parameters remained elevated due to TNFR2 neutralization. Diminished IL-10 and IFN-γ levels as a result of TNFR2 neutralization at early and later phase of infection respectively might be responsible for these contrasting effects. Overall, it can be suggested that administration of MMP-2 inhibitor and TNFR2 antibody in combination is protective against the inflammation and tissue destruction associated with S. aureus infection during the arthritic episode.
Literatur
7.
Zurück zum Zitat Nakane A, Okamoto M, Asano M, Kohanawa M, Minagawa T. Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice. Infect Immun. 1995;63(4):1165–72.PubMedPubMedCentral Nakane A, Okamoto M, Asano M, Kohanawa M, Minagawa T. Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice. Infect Immun. 1995;63(4):1165–72.PubMedPubMedCentral
9.
Zurück zum Zitat Hultgren O, Eugster HP, Sedgwick JD, Korner H, Tarkowski A. TNF/lymphotoxin-alpha double-mutant mice resist septic arthritis but display increased mortality in response to Staphylococcus aureus. J Immunol. 1998;161(11):5937–42.PubMed Hultgren O, Eugster HP, Sedgwick JD, Korner H, Tarkowski A. TNF/lymphotoxin-alpha double-mutant mice resist septic arthritis but display increased mortality in response to Staphylococcus aureus. J Immunol. 1998;161(11):5937–42.PubMed
10.
Zurück zum Zitat Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15(1):49–60.CrossRefPubMed Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15(1):49–60.CrossRefPubMed
21.
Zurück zum Zitat Han YP, Tuan TL, Wu H, Hughes M, Garne WL. TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP. J Cell Sci. 2001;114(Pt 1):131–9.PubMedPubMedCentral Han YP, Tuan TL, Wu H, Hughes M, Garne WL. TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP. J Cell Sci. 2001;114(Pt 1):131–9.PubMedPubMedCentral
25.
Zurück zum Zitat Kanangat S, Postlethwaite A, Hasty K, Kang A, Smeltzer M, Appling W, et al. Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts by Staphylococcus aureus: implications in the pathogenesis of septic arthritis and other soft tissue infections. Arthritis Res Ther. 2006;8(6):R176. https://doi.org/10.1186/ar2086.CrossRefPubMedPubMedCentral Kanangat S, Postlethwaite A, Hasty K, Kang A, Smeltzer M, Appling W, et al. Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts by Staphylococcus aureus: implications in the pathogenesis of septic arthritis and other soft tissue infections. Arthritis Res Ther. 2006;8(6):R176. https://​doi.​org/​10.​1186/​ar2086.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Sen R, Das D, Bishayi B. Staphylococcal catalase regulates its virulence and induces arthritis in catalase deficient mice. Indian J Physiol Pharmacol. 2009;53(4):307–17.PubMed Sen R, Das D, Bishayi B. Staphylococcal catalase regulates its virulence and induces arthritis in catalase deficient mice. Indian J Physiol Pharmacol. 2009;53(4):307–17.PubMed
34.
Zurück zum Zitat Yao L, Berman JW, Factor SM, Lowy FD. Correlation of histopathologic and bacteriologic changes with cytokine expression in an experimental murine model of bacteremic Staphylococcus aureus infection. Infect Immun. 1997;65(9):3889–95.PubMedPubMedCentral Yao L, Berman JW, Factor SM, Lowy FD. Correlation of histopathologic and bacteriologic changes with cytokine expression in an experimental murine model of bacteremic Staphylococcus aureus infection. Infect Immun. 1997;65(9):3889–95.PubMedPubMedCentral
39.
Zurück zum Zitat McCann FE, Perocheau DP, Ruspi G, Blazek K, Davies ML, Feldmann M. Selective tumor necrosis factor receptor I blockade is antiinflammatory and reveals immunoregulatory role of tumor necrosis factor receptor II in collagen-induced arthritis. Arthritis Rheumatol. 2014;66(10):2728–38. https://doi.org/10.1002/art.38755.CrossRefPubMed McCann FE, Perocheau DP, Ruspi G, Blazek K, Davies ML, Feldmann M. Selective tumor necrosis factor receptor I blockade is antiinflammatory and reveals immunoregulatory role of tumor necrosis factor receptor II in collagen-induced arthritis. Arthritis Rheumatol. 2014;66(10):2728–38. https://​doi.​org/​10.​1002/​art.​38755.CrossRefPubMed
40.
Zurück zum Zitat Mal P, Dutta K, Bandyopadhyay D, Basu A, Khan R, Bishayi B. Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines. Inflamm Res. 2013;62(3):259–73. https://doi.org/10.1007/s00011-012-0574-z.CrossRefPubMed Mal P, Dutta K, Bandyopadhyay D, Basu A, Khan R, Bishayi B. Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines. Inflamm Res. 2013;62(3):259–73. https://​doi.​org/​10.​1007/​s00011-012-0574-z.CrossRefPubMed
41.
Zurück zum Zitat Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.PubMed Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.PubMed
48.
Zurück zum Zitat Colowick SP, Kaplan NO, Absolom DR. Basic methods for the study of phagocytosis. In: Sabato GD, Everse J, editors. Methods in enzymology: part J. Immunochemical techniques. New York: Academic; 1986. p. 160. Colowick SP, Kaplan NO, Absolom DR. Basic methods for the study of phagocytosis. In: Sabato GD, Everse J, editors. Methods in enzymology: part J. Immunochemical techniques. New York: Academic; 1986. p. 160.
49.
Zurück zum Zitat Chandrasekhar AN. Infection and arthritis. J Assoc Physicians India. 2006;54(Suppl):27–31.PubMed Chandrasekhar AN. Infection and arthritis. J Assoc Physicians India. 2006;54(Suppl):27–31.PubMed
62.
Zurück zum Zitat Chitko-McKown CG, Ruef BJ, Rice-Ficht AC, Brown WC. Interleukin-10 downregulates proliferation and expression of interleukin-2 receptor p55 chain and interferon-gamma, but not interleukin-2 or interleukin-4, by parasite-specific helper T cell clones obtained from cattle chronically infected with Babesia bovis or Fasciola hepatica. J Interf Cytokine Res. 1995;15(10):915–22.CrossRef Chitko-McKown CG, Ruef BJ, Rice-Ficht AC, Brown WC. Interleukin-10 downregulates proliferation and expression of interleukin-2 receptor p55 chain and interferon-gamma, but not interleukin-2 or interleukin-4, by parasite-specific helper T cell clones obtained from cattle chronically infected with Babesia bovis or Fasciola hepatica. J Interf Cytokine Res. 1995;15(10):915–22.CrossRef
65.
Zurück zum Zitat Tartaglia LA, Pennica D, Goeddel DV. Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J Biol Chem. 1993;268(25):18542–8.PubMed Tartaglia LA, Pennica D, Goeddel DV. Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J Biol Chem. 1993;268(25):18542–8.PubMed
69.
Zurück zum Zitat Mirshafiey A, Mohsenzadegan M. The role of reactive oxygen species in immunopathogenesis of rheumatoid arthritis. Iran J Allergy Asthma Immunol. 2008;7(4):195–202.PubMed Mirshafiey A, Mohsenzadegan M. The role of reactive oxygen species in immunopathogenesis of rheumatoid arthritis. Iran J Allergy Asthma Immunol. 2008;7(4):195–202.PubMed
Metadaten
Titel
Dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus induced septic arthritis correlating alteration in the level of interferon gamma and interleukin-10 in terms of TNFR2 blocking
verfasst von
Sahin Sultana
Rajen Dey
Biswadev Bishayi
Publikationsdatum
07.12.2017
Verlag
Springer US
Erschienen in
Immunologic Research / Ausgabe 1/2018
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-017-8979-y

Weitere Artikel der Ausgabe 1/2018

Immunologic Research 1/2018 Zur Ausgabe

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.