PPAR-Gamma Agonist Pioglitazone Reduced CD68+ but Not CD163+ Macrophage Dermal Infiltration in Obese Psoriatic Patients

Abstract

Background. Macrophages are of great importance in the development of obesity and psoriasis. Signaling via PPAR-γ in certain macrophage populations is associated with M2-like features and anti-inflammatory profile. In this research, we evaluated the anti-inflammatory action of pioglitazone by the immunohistochemical study of M1 and M2 macrophages in psoriasis-affected skin in obese patients. Methods. We used immunohistochemistry to characterize CD68+ and CD163+ macrophages and pathomorphological description of skin biopsy, obtained from 6 obese psoriatic patients before and after treatment with 15, 30, and 45 mg pioglitazone, once a day during 6 months. Two patients with conventional therapy and without pioglitazone served as control. Results. Generally, CD163+ cell quantities in psoriasis-affected skin significantly dominated over CD68+ before and after all treatment regiments. Among patients who received pioglitazone, some of them clearly responded to treatment from lowest to highest doses by decreasing CD68+ cells. In the group with 30 mg pioglitazone regiment, we detected a significant reduction of CD68+ cells in dermal infiltrates: CI 95% (16–32) before versus CI 95% (2–7) after treatment. Pioglitazone dose escalation led to certain normalization of skin morphology. Conclusion. The immunohistochemical study allows us to show the anti-inflammatory effect of pioglitazone in psoriatic obese patients, which can be mediated by reducing the number of СD68+ macrophages, but not СD163+ macrophages, in the affected dermis.

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

“…The synthetic ligands mainly include thiazolidinediones (troglitazone, rosiglitazone, and pioglitazone), nonsteroidal anti-inflammatory drugs, and leukotriene D4 receptor antagonists. 19 The N-terminal domain of PPAR-γ contains a protein kinase phosphorylation site that can be activated by mitogens. PPAR-γ, after being activated by ligands, forms a heterodimer with the retinoic acid receptor (RXR), which then binds with the peroxisome proliferator response element (PPRE) of the target gene promoter to activate target gene transcription of factors that have a variety of biological functions.…”

Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors

“…A case-controlled study among 45 Egyptian psoriatic patients showed the statistically significant association of the Ala allele of the PPAR-γ gene (Pro12Ala polymorphism) with obesity and psoriasis occurrence, although no correlation with MS incidence was found [77]. Additionally, a pilot study carried out in the obese psoriatic patients demonstrated the anti-inflammatory skin effect of the orally administered PPAR-γ agonist (pioglitazone), which was confirmed by the immunohistochemical detection [78].…”

Cellular based immunotherapy for primary liver cancer

“…These cell interaction networks and specific molecules suggest optimizational targets for PLC immunotherapy. Hepatic macrophages play crucial roles in hepatocarcinogenesis, both the positive and negative side with signal induced differential phenotypes to our knowledge, such as negatively releasing tumor promoting cytokines in pre-metastatic niche formation and extravasation, positively eliminating hepatoma cells by phagocytosis in cancer cell arrival stage [ 127 – 130 ]. CD169 + macrophage subpopulations were found to enhance the cytotoxicity and amplification capability of CD8 + T cells against HCC under anti-CD3 irritation, and exerted suppressive effects on tumor progression [ 131 ].…”