Sarcoidosis is a multisystem granulomatous disease of unknown etiology that primarily affects the lungs. Our previous work indicates that activation of p38 plays a pivotal role in sarcoidosis inflammatory response. Therefore, we investigated the upstream kinase responsible for activation of p38 in sarcoidosis alveolar macrophages (AMs) and PBMCs. We identified that sustained p38 phosphorylation in sarcoidosis AMs and PBMCs is associated with active MAPK kinase 4 but not with MAPK kinase 3/6. Additionally, we found that sarcoidosis AMs exhibit a higher expression of IRAK1, IRAK-M, and receptor interacting protein 2 (Rip2). Surprisingly, ex vivo treatment of sarcoidosis AMs or PBMCs with IRAK1/4 inhibitor led to a significant increase in IL-1β mRNA expression both spontaneously and in response to TLR2 ligand. However, a combination of Rip2 and IRAK-1/4 inhibitors significantly decreased both IL-1β and IL-6 production in sarcoidosis PBMCs and moderately in AMs. Importantly, a combination of Rip2 and IRAK-1/4 inhibitors led to decreased IFN-γ and IL-6 and decreased percentage of activated CD4(+)CD25(+) cells in PBMCs. These data suggest that in sarcoidosis, both pathways, namely IRAK and Rip2, are deregulated. Targeted modulation of Rip2 and IRAK pathways may prove to be a novel treatment for sarcoidosis.
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http://dx.doi.org/10.4049/jimmunol.1600258 | DOI Listing |
Proc Natl Acad Sci U S A
December 2024
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Physiol Rep
November 2024
Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, USA.
Ann Med Surg (Lond)
September 2024
Traditional and Complementary Medicine Research Center, Department of Gynecology, Arak University of Medical Sciences, Arak, Iran.
Objective: Oxidative stress and inflammation play a vital function in the pathophysiology of polycystic ovary syndrome (PCOS) and infertility. The aim of this work was to control the impacts of vitamin D intake on metabolic profiles in infertile subjects with PCOS.
Trial Design And Methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 40 infertile women with PCOS.
iScience
August 2024
Unit of Basic and Applied Sciences, Department of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy.
The paracrine crosstalk between amniotic-derived membranes (AMs)/epithelial cells (AECs) and immune cells is pivotal in tissue healing following inflammation. Despite evidence collected to date, gaps in understanding the underlying molecular mechanisms have hindered clinical applications. The present study represents a significant step forward demonstrating that amphiregulin (AREG) orchestrates the native immunomodulatory functions of amniotic derivatives via the COX-2/PGE/EP4 axis.
View Article and Find Full Text PDFAnn Med Surg (Lond)
August 2024
Department of Biology, University of Balamand, Balamand, Lebanon.
Background: Atherosclerosis, a chronic inflammatory disease impacting arteries, is closely linked to cardiovascular conditions. Dyslipidemia, marked by high low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and increased plasma triglycerides, is a key risk factor. Atherogenesis begins when modified lipoproteins like oxidized LDL (ox-LDL) activate the immune system.
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