Journal List > J Rheum Dis > v.24(1) > 1064319

Lee, Choi, Hwang, and Chang: Interleukin-32 Gamma as a New Face in Inflammatory Bone Diseases

Abstract

Interleukin-32 (IL-32), a recently identified pro-inflammatory cytokine, is involved in the pathogenesis and progression of infections, cancer, chronic inflammation, and autoimmune disease. IL-32γ is the most active isoform in cell death and cell activation among nine distinct isoforms of IL-32. IL-32γ potentiates both osteogenic and osteoclastogenic capacities, and is critical in the coupling of bone resorption and bone formation for maintenance of bone homeostasis. IL-32γ is strongly associated with inflammatory bone disorders such as rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. In this review, we summarize current research on the role of IL-32γ in inflammatory bone disorders, highlighting this cytokine as a novel target for prognostic marker and control of these diseases.

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Figure 1.
Molecular mechanisms of interleukin (IL)-32γ-me-diated bone metabolism. IL-32γ increases the level of Dik-koprf-1 (DKK-1)-targeting miR-29a, leading to osteoblast differentiation and subsequent increase in bone formation. Simultaneously, IL-32γ enhances receptor activator of nuclear factor-kappa B ligand (RANKL) production to activate osteoclast differentiation.
jrd-24-14f1.tif
Figure 2.
The effects of interleukin (IL)-32γ on bone remodeling in ankylosing spondylitis and osteoporosis. (A) Normal spine remodeling is balanced by the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. In the spinal joints of patients with ankylosing spondylitis, locally elevated IL-32γ suppresses Dikkoprf-1 (DKK-1), a Wnt inhibitor in the synovium, which enables differentiation of osteoblast and subsequent new abnormal bone formation; this effect overshadows the effect of IL-32γ on receptor activator of nuclear factor-kappa B ligand (RANKL)-mediated osteoclast differentiation. (B) Diminished level of systemic IL-32γ in osteoporosis patients results in elevated expression of DKK-1, which leads to low bone mass and high fracture risk; however, there are no significant differences in bone marrow IL-32γ level between osteoporotic hip fracture patients and no-fracture patients. TNF-α: tumor necrosis factor-α.
jrd-24-14f2.tif
Table 1.
Diseases with known interleukin (IL)-32 involvement in pathogenicity
Diseases IL-32 expression Study
Viral infection Anti-viral responses against vesicular stomatitis virus (VSV), influenza A virus, herpes simplex virus 2 (HSV-2), Epstein-Barr virus (EBV), human immunodeficiency virus-1 (HIV-1) [26-30]
Bacterial infection Protection against Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium leprae [31-33]
Cancer Increased IL-32 level in gastric cancer, lung cancer, hepatocellular carcinoma, pancreatic cancer, clear cell renal cell carcinoma (CCRCC) [34-38]
Chronic inflammation and autoimmune disease Inflammatory bone disease Elevated IL-32 level in chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis (CRS), inflammatory bowel disease Rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoporosis [3-5][9,13,39,40]
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