Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation

Abstract

SUMMARYCytokines are key modulators of the immune responses that take place in the inflamed synovium of arthritis patients. Consequently, substances that can reverse the inflammatory profile of the inflamed joint are potential tools for clinical management of the disease. Mycobacterial heat shock protein 70 (MTBHSP70) has been found to protect rats from experimentally induced arthritis through the induction of interleukin (IL)-10-producing T cells. In this study, we have demonstrated that MTBHSP70 induces IL-10 production in synoviocytes from arthritis patients and peripheral blood monoculear cells (PBMCs) from both patients and healthy controls. IL-10 production was accompanied by a decrease in tumour necrosis factor (TNF)-a production by synovial cells. Separation studies showed that the target cells were mainly monocytes. Accordingly, we observed that MTBHSP70 delayed maturation of murine bone marrow-derived dendritic cells. Our results suggest that MTBHSP may act on antigen-presenting cells (APCs) to modulate the cytokine response in arthritis and support an anti-inflammatory role for this protein, suggesting that it may be of therapeutic use in the modulation of arthritis.

Gedunin Binds to Myeloid Differentiation Protein 2 and Impairs Lipopolysaccharide-Induced Toll-Like Receptor 4 Signaling in Macrophages

“…Overexpression or induction of intracellular Hsp70 (by stress or by Hsp70-inducing compounds) has been shown to decrease nuclear NFkB translocation, inducible nitric oxide synthase expression, and production of TNF-a, IL-6, IL-1b, and NO Dokladny et al, 2010;Kim et al, 2012;Muralidharan et al, 2014). Accordingly, it has been demonstrated that extracellular Hsp70 diminishes LPS-induced TNF-a by bone marrow-derived dendritic cells in vitro and induces IL-10 production by synovial cells from patients with arthritis (Detanico et al, 2004). The anti-inflammatory cytokine IL-10 suppresses LPS-induced macrophage activation by inhibiting the expression of specific TLR-induced proinflammatory genes referred to as "IL-10 counter-regulated genes" (Moore et al, 1993;Cardwall and Weaver, 2014).…”

Heat Shock Protein 70B′ (HSP70B′) Expression and Release in Response to Human Oxidized Low Density Lipoprotein Immune Complexes in Macrophages

“…The anti-inflammatory cytokine, IL-10, has been shown to be cytoprotective in macrophages (51) and induced by the addition of exogenous HSP70 in synovial cells (52,53), suggesting that HSPs play an active role in suppressing inflammation by the regulation of IL-10. Here we provide evidence that secretion of IL-10 may be regulated by HSP70BЈ.…”

Differential pattern of cytokine expression by macrophages infectedin vitrowith differentMycobacterium tuberculosisgenotypes

“…However, the in vivo studies also showed a mild early IFN-g expression, which is in disagreement with our in vitro results that showed high p40 IL-12/Il-23 and IL-18 expression. Thus, other unknown factors could be contributing to prevent [17] and/or some mycobacterial components might also modify it, being expressed during this phase of infection [18,19]. One possibility whereby Mtb strains might modulate differential expression of cytokines and iNOS in BMDM could be through bacterial components interacting with macrophage receptors.…”