Docosahexaenoic Acid Suppresses Silica-Induced Inflammasome Activation and IL-1 Cytokine Release by Interfering With Priming Signal

Occupational exposure to respirable crystalline silica (cSiO2) has been etiologically linked to human autoimmunity. Intranasal instillation with cSiO2 triggers profuse inflammation in the lung and onset of autoimmunity in lupus-prone mice; however, dietary supplementation with the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) abrogates these responses. Inflammasome activation, IL-1 cytokine release, and death in alveolar macrophages following cSiO2 exposure are early and critical events that likely contribute to triggering premature autoimmune pathogenesis by this particle. Here we tested the hypothesis that DHA suppresses cSiO2-induced NLRP3 inflammasome activation, IL-1 cytokine release, and cell death in the macrophage. The model used was the murine macrophage RAW 264.7 cell line stably transfected with the inflammasome adapter protein ASC (RAW-ASC). Following priming with LPS, both the canonical activator nigericin and cSiO2 elicited robust inflammasome activation in RAW-ASC cells, as reflected by IL-1β release and caspase-1 activation. These responses were greatly diminished or absent in wild-type RAW cells. In contrast to IL-1β, cSiO2 induced IL-1α release in both RAW-ASC and to a lesser extent in RAW-WT cells after LPS priming. cSiO2-driven effects in RAW-ASC cells were confirmed in bone-marrow derived macrophages. Pre-incubating RAW-ASC cells with 10 and 25 μM DHA for 24 h enriched this fatty acid in the phospholipids by 15- and 25-f...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Publication date: Available online 19 October 2019Source: Autoimmunity ReviewsAuthor(s): David S. Pisetsky, Xavier Bossuyt, Pier Luigi MeroniAbstractSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease with highly variable clinical and immunological manifestations. In the classification of patients with this condition, the presence of an antinuclear antibody (ANA) is an important element, with new criteria from the American College of Rheumatology and European League against Rheumatism positioning ANA positivity by an immunofluorescence assay on HEp2-cells (HEp2-IFA) or by an equivalent solid phase assay a...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Conclusion: CXorf21 is more highly expressed in female compared to male cells and is involved in a sexually dimorphic response to TLR7 activation. In addition, CXorf21 expression regulates lysosomal pH in a sexually dimorphic manner. Thus, sexually dimorphic expression of CXorf21 skews cellular immune responses in manner consistent with expected properties of a mediator of the X chromosome dose risk in SLE and pSS.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study included children who were followed regularly in our lupus clinic with proved full house glomerular immune deposits nephritis and antinuclear (ANA), or anti-double-stranded DNA (dsDNA). They were compared with patients who diagnosed with cSLE with and without biopsy proven nephritis, based on Systemic Lupus International Collaborating (SLICC). The comparative group selected by systematic sampling from our cSLE database; the first patient was chosen randomly, and the subsequent patients chosen at intervals of three. The two groups were compared in respect to demographic data, clinical and laboratory findings, and...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Lupus érythémateux systémique. Rev Med Interne. 2019 Sep;40S:S14-S19 Authors: Saadoun D, Desbois AC PMID: 31627799 [PubMed - in process]
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research
In this study, we carried out qualitative and quantitative analysis of the donkey whey proteome using a label-free proteomic approach, combined with parallel reaction monitoring (PRM) as a validation method. A total of 300 whey proteins were identified in donkey colostrum (DC) and donkey mature (DM) milk, of which 18 were differentially expressed (P
Source: Food Research International - Category: Food Science Source Type: research
Conclusions: 1. Clinical suspicion of APS requires careful diagnostic testing. Because of inadequate diagnostic workup, many patients may not even have an APS, and these patients could be adequately treated with a DOAC. 2. Patients with single or double positive antiphospholipid antibodies but without positive LA may have a comparably low thrombotic risk and may also be treated with a DOAC in venous TE - sufficient evidence for that conclusion is not yet available but is suggested by the results of meta-analyses. 3. Triple positive patients or those with APS who suffered from arterial thromboembolism have a very high ...
Source: VASA. Zeitschrift fur Gefasskrankheiten. Journal for Vascular Diseases - Category: Surgery Authors: Tags: Vasa Source Type: research
CONCLUSION: The histomorphological indexes in lupus nephritis are easily obtainable, can predict renal outcomes and may help in the management of such patients. PMID: 31625875 [PubMed - in process]
Source: Acta Medica Portuguesa - Category: General Medicine Tags: Acta Med Port Source Type: research
A recent study in The Journal of Rheumatology sheds light on the importance of preconceptional cardiovascular health in women with systemic lupus erythematosus. Although many questions remain, improved cardiovascular health measures seem to positively affect pregnancy outcomes, suggesting a potential role for preconception cardiovascular interventions.1 Women with lupus now have healthier pregnancies than in the... [Read More]
Source: The Rheumatologist - Category: Rheumatology Authors: Tags: Conditions Research Reviews SLE (Lupus) cardiovascular pregnancy Source Type: research
Authors: Zhang R, Li Y, Pan B, Li Y, Liu A, Li X Abstract Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterized by overactive inflammation and aberrant activation of lymphocytes. Chemokine C-X-C motif ligand 10 (CXCL10) has an important role in the initiation and deterioration of SLE. However, the expression levels of CXCL10 mRNA in T-helper (Th) cells and B lymphocytes from SLE patients have remained elusive. In the present study, a Bioinformatics analysis of differentially expressed gene (DEG) profiles obtained from RNA sequencing data for three matched samples was performed to ex...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
In conclusion, TNF-α − 863A allele (rs1800630) polymorphism is associated with increased risk of nephritis in South Indian SLE patients. We also found an interaction between HLA-DRB1*07 allele with TNF-α − 863 C/A promoter polymorphism giving supportive evidence for the tig ht linkage disequilibrium between TNF-α promoter SNPs and MHC class II DRB1 alleles.
Source: Indian Journal of Clinical Biochemistry - Category: Biochemistry Source Type: research
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