Fasciola helminth defense molecule‐1 protects against experimental arthritis by inhibiting osteoclast formation and function without modulating the systemic immune response

Abstract

An inverse correlation between helminth infection and the autoimmune disease appears to be contributed by the anti-inflammatory factors produced by these organisms. Suppressing osteoclast function without affecting the systemic immunological response is an emerging therapeutic strategy for rheumatoid arthritis (RA). We observed that a synthetic peptide corresponding to 34 amino acids of C-terminal sequence of Fasciola helminth defense molecule-1 (C-FhHDM-1) inhibited RANKLinduced osteoclast formation and lysosomal acidification with an attendant upregulation of sequestome1/p62, a negative regulator of NF-κB expression. C-FhHDM-1 also suppressed RANKL production from osteoblasts. Macrophages are the major inflammatory cells in the joints of RA and C-FhHDM-1 suppressed ICAM-1 (an inflammatory surrogate) expression in these cells. In a murine model of collagen II-induced arthritis (CIA), C-FhHDM-1 improved clinical score, protected against cartilage destruction, and maintained bone mass and bone architecture of joints compared with the CIA group. C-FhHDM-1 suppressed the CIA-induced expression of TNF, IL-17, and IFN-γ in joints but not their serum levels. The peptide also had no effect on the CIA-induced suppression of T regulatory response. We conclude that C-FhHDM-1 has a joint-specific protective effect in experimental arthritis without mitigating systemic inflammation, and thus could become an adjuvant anti-arthritis therapy to prevent RA-induced osteopenia.

Can quantitative surface antigen levels and systemic immune-inflammation index be predictive as a new indicator for the initiation of treatment in chronic hepatitis b?

“…In benign situations like infections and inflammation, the systemic immune response is essential. Recent research suggests its diagnostic utility in high-grade tumors [66][67][68]. Qi et al established the SIRI as a new inflammatory marker.…”

A standardized extract of Coleus forskohlii root protects rats from ovariectomy-induced loss of bone mass and strength, and impaired bone material by osteogenic and anti-resorptive mechanisms

“…After treatment, calvaria were removed and processed for RNA isolation by trizol method (30). qPCR was performed by SYBR green chemistry (Thermo Fisher Scientific, Ealtham, MA, USA) for the quantitative determination of bone morphogenetic protein 2 (BMP2), type 1 collagen (Col I), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) as described previously (31). cDNA was synthesized by using 2mg RNA (Cat no.…”

Bone erosion in inflammatory arthritis is attenuated by Trichinella spiralis through inhibiting M1 monocyte/macrophage polarization

“…ES-62, a glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae inhibits functional OC differentiation by induction of anti-oxidant response gene expression, thereby resulting in reduction of the reactive oxygen species production that is necessary for the osteoclastogenesis (Doonan et al, 2018). Additionally, a synthetic peptide of secretory protein from Fasciola hepatica inhibited the RANKL-induced differentiation of macrophages to OCs and lysosomal acidification of differentiated OCs by inhibiting the action of vATPase which trigger bone resorption (Khan et al, 2020). In this study, we found that LPS enhanced osteoclastogenesis from RAW264.7 macrophages upon RANKL stimulation in vitro, whereas IL-4 had little effect on RANKL-induced OC formation, indicative of a greater osteoclastogenic differentiation ability of M1 macrophages compared to M2 phenotype (Figure S2).…”

“…Studies in animal models have demonstrated that intentional exposure to helminths or helminth-derived products can effectively alleviate inflammatory arthritis by inducing Th2 responses or FOXP3 + T regulatory cells (Barranco, 2016;Chen et al, 2016). Recent studies have shown that helminth infections or helminth products are not only capable of suppressing arthritic inflammation but can also protect against arthritis-associated bone erosion in animal models (Doonan et al, 2018;Khan et al, 2020;Sarter et al, 2017). Although macrophages play a crucial role in osteoclastic activity, the mechanism that helminths target macrophage to inhibit bone erosion in inflammatory arthritis is not well understood.…”