Increased IL- 36γ in visceral adipose tissue as a key mediator of obesity-driven inflammation in colon cancer
Year: 2025
Type: article
Study design: Observational Study
Abstract: Dysfunctional adipose tissue (AT) in the context of obesity promotes a chronic inflammatory state, associated with worse cancer progression and prognosis. Interleukin (IL)-36γ is a proinflammatory factor increased in obesity. The aim was to analyse the role of IL-36γ in colon cancer (CC) development in patients with obesity. Samples obtained from 74 volunteers (27 with normal weight (NW) and 47 with obesity (OB)) were used in a case-control study. Participants were also subclassified according to the presence of CC (45 without and 29 with CC). HT-29 cells were treated with pro-inflammatory factors, adipocyte conditioned media (ACM) and IL-36γ to evaluate the expression levels of inflammation- and extracellular matrix (ECM) remodelling-related molecules. Increased gene expression levels of IL36G and IL36R in visceral AT from patients with OB and CC were found. Moreover, mRNA levels of IL36G were significantly associated with the gene expression levels of its receptor and relevant genes involved in AT inflammation (ASC, IL1B and NLRP6). Consistently, IL36G expression was upregulated by hypoxia, inflammation-related factors (LPS, TNF-α and leptin) and by the adipocyte secretome from patients with obesity in HT-29 cancer cells. Furthermore, we revealed that IL-36γ increased the gene expression levels of inflammation-related genes (IL36G, IL1 A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells. Increased gene expression levels of IL36G in VAT from patients with OB and CC may promote a pro-inflammatory microenvironment favourable for tumour progression and migration. KEY MESSAGES: Obesity and colon cancer increase gene expression levels of IL36G and IL36R in visceral adipose tissue. Hypoxia, inflammation-related factors and the adipocyte secretome from patients with obesity upregulate mRNA levels of IL36G in HT-29 cancer cells. IL-36γ increase the gene expression levels of inflammation-related genes (IL36G, IL1A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells.
Source: Journal of Molecular Medicine
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Awards: Papel del eje MMP14/GDF15 en las alteraciones metabólicas relacionadas con la obesidad y su interacción con la edad, Papel de los péptidos antimicrobianos en la regulación de la integridad de la barrera intestinal y la inflamación del tejido adiposo en un contexto de obesidad y diabetes tipo 2, Cambios en la inflamación del tejido adiposo asociada a la obesidad y sus comorbilidades tras cirugía bariátrica inducidos por la proteína 1 similar a la folistatina (FSTL1)
OpenAlex ID: W4409719784