Increased Adipose Tissue Expression of IL-23 Associates with Inflammatory Markers in People with High LDL Cholesterol

Kochumon, Shihab; Hasan, Amal; Al-Rashed, Fatema; Sindhu, Sardar; Thomas, Reeby; Jacob, Texy; Al-Sayyar, Amnah; Arefanian, Hossein; Madhoun, Ashraf Al; Al-Ozairi, Ebaa; Alzaïd, Fawaz; Koistinen, Heikki A.; Al-Mulla, Fahd; Tuomilehto, Jaakko; Ahmad, Rasheed

doi:10.3390/cells11193072

Cited by 11 publications

(10 citation statements)

References 61 publications

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“…Adiponectin may be correlated with IL-23 and IL-17. Kochumon and colleagues found negative correlations between IL-23 gene expression and the level of adiponectin in patients with high levels of LDL cholesterol [ 126 ]. Furthermore, Shibata et al used an adiponectin knockdown and wild-type mice to evaluate the expression of psoriasis cytokines.…”

Section: Adiponectinmentioning

confidence: 99%

The Role of Adipokines in the Pathogenesis of Psoriasis

Kiełbowski

Bakinowska

Ostrowski

et al. 2023

IJMS

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Psoriasis is a chronic and immune-mediated skin condition characterized by pro-inflammatory cytokines and keratinocyte hyperproliferation. Dendritic cells, T lymphocytes, and keratinocytes represent the main cell subtypes involved in the pathogenesis of psoriasis, while the interleukin-23 (IL-23)/IL-17 pathway enhances the disease progression. Human adipose tissue is an endocrine organ, which secretes multiple proteins, known as adipokines, such as adiponectin, leptin, visfatin, or resistin. Current evidence highlights the immunomodulatory roles of adipokines, which may contribute to the progression or suppression of psoriasis. A better understanding of the complexity of psoriasis pathophysiology linked with adipokines could result in developing novel diagnostic or therapeutic strategies. This review aims to present the pathogenesis of psoriasis and the roles of adipokines in this process.

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Section: Adiponectinmentioning

confidence: 99%

The Role of Adipokines in the Pathogenesis of Psoriasis

Kiełbowski

Bakinowska

Ostrowski

et al. 2023

IJMS

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“…These associations may be attributed to specific inflammatory markers upregulated in patients with such baseline factors. For instance, interleukin (IL) 23 has been found to be elevated in smokers and patients with dyslipidemia ( 34 , 35 ). This is interesting as IL-23 is a pro-inflammatory cytokine that plays an active role in activating T-helper 17 (Th17) cells.…”

Section: Discussionmentioning

confidence: 99%

Association between immune checkpoint inhibitor medication and uveitis: a population-based cohort study utilizing TriNetX database

Kuo,

Chen,

Hsu

et al. 2024

Front. Immunol.

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ObjectiveTo explore the associations between the use of immune checkpoint inhibitors (ICIs) and the risk of developing uveitis among cancer patients.MethodsCancer patients who received ICI therapy and a comparison group of cancer patients who did not receive ICI therapy were retrospectively recruited from the TriNetX electronic heath-record registry. The outcome of interest was the development of new-onset uveitis. Propensity score matching based on a 1:1 ratio was conducted in order to reduce bias. Multi-variate cox proportional hazard models and Kaplan Meier method were also utilized to assess for the risk of uveitis among cancer patients who received ICI therapy.Results71931 cancer patients (54.7% male; 76.5% white; mean age at index 63.6 ± 12.2 years) who received ICI treatment (ICI group) and 71931 cancer patients (54.7% male; 77% white; mean age at index 63.5 ± 12.4 years) who never received ICI (comparison group) were recruited. Associated Kaplan-Meier curves showed significantly increased uveitis risk among the ICI group for all follow-up years (p<0.001). The risk of uveitis was also higher among the ICI group during the 144-month follow-up period with a hazard ratio (HR) of 2.39 (95% CI: 2.07-2.75). Increased risk for specific uveitis diseases, such as iridocyclitis, chorioretinal inflammation, retinal vasculitis, unspecified purulent endophthalmitis, pan-uveitis and sympathetic uveitis were found. Subgroup analysis demonstrated an elevated hazard ratio for the development of uveitis among ICI recipients, spanning individuals below the age of 65 as well as those aged 65 and older. The elevated hazard ratio for uveitis development among ICI recipients was also observed across all genders, among those of white and Asian ethnicities, those with smoking history, and those with comorbid conditions such as hypertension and dyslipidemia, in comparison to their non-ICI counterparts. An additional subgroup analysis on monotherapy versus combinatory ICI regimens was also conducted. Individuals who received monotherapy from the class of anti-PD-1 (HR:1.98 [CI: 1.65-2.37]) and anti-CTLA-4 (HR:5.86 [CI:1.99-17.24]) exhibited elevated hazard ratios for uveitis development compared to their non-ICI comparators. Those exposed to combinatory ICI regimens, specifically a combination of anti-PD-1 and anti-CTLA4 (HR: 5.04 [CI:3.55-7.16]), showed increased hazard ratios for uveitis development compared to their non-ICI comparators. In contrast, individuals exposed to a combination of anti-PD-1 and anti-PD-L1 (HR: 2.47 [CI:0.81-7.50]) did not demonstrate an increased risk for uveitis compared to their non-ICI comparators.ConclusionA significantly increased risk for uveitis diseases was found among the ICI group from the first year of follow-up. Increased awareness should be promoted on the occurrence of uveitis among cancer patients receiving ICI therapy.

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“…We collected AT samples (approximately 500 mg) via abdominal subcutaneous fat pad biopsy by following standard surgical procedures, as described previously [ 20 , 22 , 23 ]. Briefly, the periumbilical area was decontaminated using alcohol-soaked gauze, and then locally anesthetized using 2% lidocaine.…”

Section: Methodsmentioning

confidence: 99%

Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling

Madhoun

Kochumon

Haddad

et al. 2023

Cells

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Obesity is characterized by chronic low-grade inflammation. Obese people have higher levels of caveolin-1 (CAV1), a structural and functional protein present in adipose tissues (ATs). We aimed to define the inflammatory mediators that influence CAV1 gene regulation and the associated mechanisms in obesity. Using subcutaneous AT from 27 (7 lean and 20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor-alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). CAV1 gene expression was associated with proinflammatory cytokines and chemokines and their cognate receptors (r ≥ 0.447, p ≤ 0.030), but not with anti-inflammatory markers. CAV1 expression was correlated with CD163, indicating a prospective role for CAV1 in the adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces CAV1 gene transcription by mediating NF-κB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and the TNF-α signaling pathway is intriguing and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.

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Increased Adipose Tissue Expression of IL-23 Associates with Inflammatory Markers in People with High LDL Cholesterol

Cited by 11 publications

References 61 publications

The Role of Adipokines in the Pathogenesis of Psoriasis

The Role of Adipokines in the Pathogenesis of Psoriasis

Association between immune checkpoint inhibitor medication and uveitis: a population-based cohort study utilizing TriNetX database

Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling

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