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Silica‐Triggered Multi‐Organ Autoimmune Gene Expression in Lupus‐Prone Mice is Ablated by Docosahexaenoic Acid Consumption
Author(s) -
Bates Melissa A.,
Gilley Kristen N.,
JacksonHumbles Daven N.,
Harkema Jack R.,
Holian Andrij,
Pestka James J.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.657.21
Subject(s) - autoimmunity , docosahexaenoic acid , immunology , lupus nephritis , medicine , endocrinology , immune system , nephritis , spleen , biology , polyunsaturated fatty acid , fatty acid , disease , biochemistry
While heredity is a primary predisposing factor for autoimmunity, the exposome can critically influence latency and severity of autoimmune diseases such as systemic lupus erythematosus (SLE). We have previously demonstrated that airway exposure to the toxicant crystalline silica (cSiO 2 ) triggers early loss of self‐tolerance in the lung thereby accelerating onset of systemic autoimmunity and exacerbates glomerulonephritis in the female NZBWF1 mouse, a widely used SLE model. Remarkably, dietary supplementation with the omega‐3 polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA), abrogates cSiO 2 ‐induced lung inflammation, systemic autoimmunity and nephritis in this model. We hypothesized here that cSiO 2 ‐triggered inflammation in the lung precedes systemic autoimmunity and nephritis in NZBWF1 mice and is a primary target for the prophylactic action of DHA. Beginning at 6 wk of age, female NZBWF1 mice were fed an isocaloric AIN‐93G diet containing 0.0, 0.4, or 1.0 % DHA. Two wk later, mice were intranasally instilled with 1.0 mg cSiO 2 once per week for 4 wk and maintained on experimental diets until sacrifice. At 13, 16, 19 and 22 wk of age, cohorts were sacrificed and lung, spleen, and kidney were collected. Total RNA from these tissues for each cohort was isolated and purified, and gene expression levels were determined with the nCounter ® PanCancer Immune Profiling for mouse, a multiplexed method for immune profiling of 800 target genes. cSiO 2 ‐induced elevations in gene expression were first evident in the lung in cohorts from 13 wk and later whereas in spleen and kidney elevations were seen at 16 wk and thereafter. Genes observed to upregulated by cSiO 2 included chemotactic factors, cytokines, B cell receptors, and remarkably, genes involved in interferon regulation. Importantly, cSiO 2 ‐triggered expression of these genes was dose‐dependently suppressed by DHA in all three tissues over time. Taken together, marked attenuation cSiO 2 ‐induced elevations of inflammatory and immune genes by DHA in the lung, spleen and kidney suggests that supplementation with this omega‐3 PUFA might be used to mitigate environmental triggering of autoimmune disease. Support or Funding Information Lupus Foundation of America, Inc.