Role of IL-32 Gamma on Bone Metabolism in Autoimmune Arthritis

Abstract

IL-32 acts as a pro-inflammatory cytokine by inducing the synthesis of inflammatory molecules as well as promoting the morphological changes involved in the transformation of monocytes into osteoclasts (OCs). Evaluation of the functions of IL-32 has mainly focused on its inflammatory properties, such as involvement in the pathogenesis of various autoimmune diseases. Recently, IL-32 was shown to be involved in bone metabolism, in which it promotes the differentiation and activation of OCs and plays a key role in bone resorption in inflammatory conditions. IL-32γ also regulates bone formation in conditions such as ankylosing spondylitis and osteoporosis. In this review, we summarize the results of recent studies on the role of IL-32γ in bone metabolism in inflammatory arthritis.

Increased levels of interleukin‐32 isoforms alpha, beta, gamma, and delta in the gingival crevicular fluid and plasma of the patients with periodontitis

“…IL‐32 has nine isoforms generated by alternative splicing 11,12,15 . The four most researched isoforms IL‐32α, IL‐32β, IL‐32γ, and IL‐32δ were first described in IL‐2‐stimulated human NK cells 4 12,47 .…”

“…The four most researched isoforms IL‐32α, IL‐32β, IL‐32γ, and IL‐32δ were first described in IL‐2‐stimulated human NK cells 4 12,47 . Among these isoforms, IL‐32α is the shortest and the least active pro‐inflammatory variant contains three protein domains, domains 1, 6, and 11 that consist of 131 amino acid residues 9,15,24 . Compared to other isoforms, IL‐32 α is also the most ample cDNA clone 8 and it is expressed in various cells such as NK cells, T cells, and monocytes 10 .…”

“…The role of IL‐32 in inflammation is pleiotropic, because it is related with the enhancing both pro‐inflammatory and anti‐inflammatory cytokines 13,14 . It is stated that this property is due to its isoforms having different biological activities and properties 13,15 . The pro‐inflammatory role of IL‐32 has been well determined in various diseases including rheumatoid arthritis (RA), 16 different cancers, 12,17 pulmonary tuberculosis, 18 chronic rhinosinusitis, 19 inflammatory bowel disease, etc 20 Differently, it has been shown that IL‐32 has anti‐inflammatory properties in experimental colitis, in experimental allergic airway inflammation and in lipopolysaccharide‐induced arthritis 21‐23 .…”

Expression of interleukin-32 in bone marrow of patients with myeloma and its prognostic significance

“…This provides new prognostic information that can be used to further improve the current risk stratification strategy for MM patients. Kwon et al[17] reported that poor prognosis in patients with inflammatory diseases and autoimmune diseases had higher IL-32 expression. In a separate study, high expression of IL-32 was also found to be positively associated with metastasis and recurrence of renal cell carcinoma and gastric cancer[18].…”

Structural Characteristics of Seven IL-32 Variants

“…IL-32 is generally considered to be an inflammatory cytokine since early IL-32 research suggested that it is an inducer of TNFα. Therefore many investigators approached the effect of IL-32 in Th1 autoimmune-associated diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis (5678). The majority of clinical studies depend on the measurement of circulating IL-32 levels in the plasma or serum of patients comparing to normal individuals.…”