Interleukin-18 (IL-18), also known as interferon-gamma inducing factor is a protein which in humans is encoded by the IL18 gene. The protein encoded by this gene is a proinflammatory cytokine. Many cell types, both hematopoietic cells and non-hematopoietic cells, have the potential to produce IL-18. It was first described in 1989 as a factor that induced interferon-γ (IFN-γ) production in mouse spleen cells. Originally, IL-18 production was recognized in Kupffer cells, liver-resident macrophages. However, IL-18 is constitutively expressed in non-hematopoietic cells, such as intestinal epithelial cells, keratinocytes, and endothelial cells. IL-18 can modulate both innate and adaptive immunity and its dysregulation can cause autoimmune or inflammatory diseases. IL-18 belongs to the IL-1 superfamily and is produced mainly by macrophages but also other cell types, stimulates various cell types and has pleiotropic functions. IL-18 is a proinflammatory cytokine that facilitates type 1 responses. Together with IL-12, it induces cell-mediated immunity following infection with microbial products like lipopolysaccharide (LPS). IL-18 in combination with IL12 acts on CD4, CD8 T cells and NK cells to induce IFNγ production, type II interferon that plays an important role in activating the macrophages or other cells. The combination of this IL-18 and IL-12 has been shown to inhibit IL-4 dependent IgE and IgG1 production and enhance IgG2a production in B cells. Importantly, without IL-12 or IL-15, IL-18 does not induce IFNγ production, but plays an important role in the differentiation of naive T cells into Th2 cells and stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine.
Background References
1. Zhang X et al. IL18 signaling causes islet β cell development and insulin secretion via different receptors on acinar and β cells. Dev Cell. 2022 Jun
2. Lin T et al. NET-Triggered NLRP3 Activation and IL18 Release Drive Oxaliplatin-Induced Peripheral Neuropathy. Cancer Immunol Res. 2022 Dec
Western blot analysis of IL-18 on different lysates with Rabbit anti-IL-18 antibody (HA721537) at 1/5,000 dilution.
Lane 1: A431 (Human epidermoid carcinoma skin squamous cell) cell lysate Lane 2: HeLa (Human cervical adenocarcinoma cell) cell lysate
Lysates/proteins at 20 µg/Lane. Exposure time: 6 seconds; ECL: K1801
Blocking: 5% NFDM/TBST, 1 hour at room temperature Primary antibody: HA721537, 1/5,000 in primary antibody dilution buffer (K1803), overnight at 4 ℃ Secondary antibody: Goat anti-Rabbit IgG-HRP (HA1001), 1/50,000 in 5% NFDM/TBST, 1 hour at room temperature
Predicted band size: 22 kDa Observed band size: 22 kDa
Flow cytometric analysis of A431 cells labeling IL-18.
Cells were fixed and permeabilized. Then stained with the primary antibody (HA721537, 1ug/ml) (red) compared with Rabbit IgG Isotype Control (green). After incubation of the primary antibody at +4℃ for an hour, the cells were stained with a iFluor™ 488 conjugate-Goat anti-Rabbit IgG Secondary antibody (HA1121) at 1/1,000 dilution for 30 minutes at +4℃. Unlabelled sample was used as a control (cells without incubation with primary antibody; black).
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