IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation

Mansoori, Mohd Nizam; Shukla, Pragya; Kakaji, Manisha; Tyagi, Abdul Malik; Srivastava, Kirti; Shukla, Manoj Kumar; Dixit, Manisha; Kureel, Jyoti; Gupta, Sushil K.; Singh, Divya

doi:10.1038/srep33680

Cited by 57 publications

(50 citation statements)

References 52 publications

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“…Micro-computed Tomography-CT determination of excised bones was carried out using Sky Scan 1076 CT scanner (Aartselaar, Belgium) using previously published protocol (10,24,36). Three samples were scanned per batch at nominal resolution pixel 18 m. Reconstruction was carried out using a modified Feldkamp algorithm using the Sky Scan Nrecon Software, which facilitates network-distributed reconstruction carried on a personal computer running simultaneously.…”

Section: Methodsmentioning

confidence: 99%

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Shukla

Mansoori

Kakaji

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangA growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined. In this report, we study the effect of IL-27 supplementation on ovariectomized estrogen-deficient mice on various immune and skeletal parameters. IL-27 treatment in ovariectomized mice suppressed Th17 cell differentiation by inhibiting transcription factor ROR␥t. Supplementation of IL-27 activates Egr-2 to induce IL-10 producing Tr1 cells. IL-27 treatment prevented the loss of trabecular micro-architecture and preservedcorticalboneparameters.IL-27alsoinhibitedosteoblastapo-ptosis through increased Egr-2 expression, which induces antiapoptotic factors like MCL-1. IL-27 suppressed osteoclastogenesis in an Egr-2-dependent manner that up-regulates Id2, the repressor of the receptor activator of nuclear factor-B ligand-mediated osteoclastogenesis. Additionally, these results were corroborated in female osteoporotic subjects where we found decreased serum IL-27 levels along with reduced Egr-2 expression. Our study forms a strong basis for using humanized IL-27 toward the treatment of post-menopausal osteoporosis.

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Section: Methodsmentioning

confidence: 99%

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Shukla

Mansoori

Kakaji

et al. 2017

Journal of Biological Chemistry

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“…In addition, signals provided by NF- κ B activators are necessary for NLRP3 inflammasome activation to produce active IL-1 β and IL-18 [ 31 ]. The NLRP3 inflammasome also potentially creates a microenvironment for Th17 cell differentiation [ 38 , 39 ]. Thus, the NLRP3 inflammasome regulated by the NF- κ B pathway, at least partially, may take part in ITP pathogenesis mediated by the dysfunction of T helper cells.…”

Section: Discussionmentioning

confidence: 99%

NF-κB-94ins/del ATTG Genotype Contributes to the Susceptibility and Imbalanced Th17 Cells in Patients with Immune Thrombocytopenia

Hua

Zhao

et al. 2018

Journal of Immunology Research

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Background The NLRP3 inflammasome plays important roles in the pathogenesis of autoimmune diseases. However, the role of the NLRP3 inflammasome in the pathophysiology of immune thrombocytopenia (ITP) remains unclear. Methods RT-PCR was used to examine the polymorphism and expression of genes involved in the NLRP3 inflammasome in ITP patients. T helper cells and apoptosis of PBMC from ITP patients were analyzed by flow cytometry. The antiplatelet autoantibodies in plasma were determined by modified monoclonal antibody-specific immobilization of platelet antigens (MAIPA). Results We found that the NF-κB-94ins/del ATTG genotype contributed to the susceptibility of ITP. Furthermore, the platelet counts of ITP patients with the WW genotype or WD genotype were lower than those with the DD genotype of NF-κB-94ins/del ATTG. Compared with controls, NF-κB gene expression was significantly decreased and WW or WD genotype ITP patients displayed higher mRNA expression than DD individuals. Similarly, the mRNA expression of NLRP3 was also increased in the WW genotype. There was a significant gene dose effect of the percentage of Th17 cells for the WW, WD, and DD genotypes (WW < WD < DD) in the unstimulated group and no significant difference was found after being stimulated. The activation of the NLRP3 inflammasome could upregulate Th17 in ITP patients. Conclusion The NF-κB-94ins/del ATTG genotype might serve as a novel biomarker and potential target for ITP.

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“…In post-menopausal osteoporosis, IL-18 blood levels are increased while those of its antagonist, IL-18BP, are decreased. According to Mansoori et al, IL-18BP enhanced murine osteoblast differentiation and inhibits the activation of NLRP3 inflammasome and caspase-1, in vitro , and improved the metabolic and bone statuses in ovariectomized rats (a rodent model of post-menopausal OP) (132). Further evidences derived from the association of NLRP3 mutations with arthropathy and OP (133) and the SIRT1-dependent inhibition of osteogenic differentiation and enhancement adipogenic differentiation, in mesenchymal stem cells (MSC), following lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation (134).…”

Section: Immuno-mediated Effects Of Exercise and Training On Bonementioning

confidence: 99%

Physical Activity and Bone Health: What Is the Role of Immune System? A Narrative Review of the Third Way

2019

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Bone tissue can be seen as a physiological hub of several stimuli of different origin (e.g., dietary, endocrine, nervous, immune, skeletal muscle traction, biomechanical load). Their integration, at the bone level, results in: (i) changes in mineral and protein composition and microarchitecture and, consequently, in shape and strength; (ii) modulation of calcium and phosphorous release into the bloodstream, (iii) expression and release of hormones and mediators able to communicate the current bone status to the rest of the body. Different stimuli are able to act on either one or, as usual, more levels. Physical activity is the key stimulus for bone metabolism acting in two ways: through the biomechanical load which resolves into a direct stimulation of the segment(s) involved and through an indirect load mediated by muscle traction onto the bone, which is the main physiological stimulus for bone formation, and the endocrine stimulation which causes homeostatic adaptation. The third way, in which physical activity is able to modify bone functions, passes through the immune system. It is known that immune function is modulated by physical activity; however, two recent insights have shed new light on this modulation. The first relies on the discovery of inflammasomes, receptors/sensors of the innate immunity that regulate caspase-1 activation and are, hence, the tissue triggers of inflammation in response to infections and/or stressors. The second relies on the ability of certain tissues, and particularly skeletal muscle and adipose tissue, to synthesize and secrete mediators (namely, myokines and adipokines) able to affect, profoundly, the immune function. Physical activity is known to act on both these mechanisms and, hence, its effects on bone are also mediated by the immune system activation. Indeed, that immune system and bone are tightly connected and inflammation is pivotal in determining the bone metabolic status is well-known. The aim of this narrative review is to give a complete view of the exercise-dependent immune system-mediated effects on bone metabolism and function.

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IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation

Cited by 57 publications

References 52 publications

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

NF-κB-94ins/del ATTG Genotype Contributes to the Susceptibility and Imbalanced Th17 Cells in Patients with Immune Thrombocytopenia

Physical Activity and Bone Health: What Is the Role of Immune System? A Narrative Review of the Third Way

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