Data from: Dietary docosahexaenoic acid supplementation inhibits acute pulmonary transcriptional and autoantibody responses to a single crystalline silica exposure in lupus-prone mice

Short-term repeated intranasal exposure crystalline silica (cSiO2), a
known human autoimmune trigger, induces uncontrolled inflammation,
upregulated IFN-stimulated gene expression, diverse autoantibody
production, and glomerulonephritis in lupus-prone female NZBWF1 mice.
Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid
(DHA) prevents subchronic cSiO2 triggering of these lupus hallmarks. To
understand how this intervention impacts acute effects of cSiO2, we fed
NZBWF1 mice control (CON) or DHA-containing diet, subjected them to a
single acute intranasal instillation of 2.5 mg cSiO2, then compared
pulmonary inflammatory/autoimmune responses and autoimmune-related gene
expression in experimental cohorts terminated at 7 and 28 d
post-instillation (PI). Acute cSiO2 exposure of CON-fed mice elicited
decreased macrophage and increased neutrophil numbers at 7 d PI, whereas
at 28 d PI, CON-fed mice treated with particle displayed elevated total
cell, macrophage, neutrophil, and lymphocyte counts. In contrast, DHA-fed
mice treated with cSiO2 exhibited less macrophage loss at 7 d PI and
reduced total cell, macrophage, and lymphocyte accumulation at 28 d PI.
Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) of
lung sections suggested that cSiO2 induced more robust cell death at 7 d
PI in CON-fed than DHA-fed mice. Targeted multiplex ELISA of lung extracts
showed that at 28 d PI, cSiO2 induced higher concentrations of
inflammation-associated cytokines (IL-1α, IL-6, and GM-CSF) and
IFN-stimulated chemokines (CCL2, CCL3, CXCL10) in the CON-fed cohort than
in the DHA-fed cohort. Autoantigen protein microarray of BALF collected at
28 d PI indicated that cSiO2 induced higher autoantibody responses for
representative nuclear, ribosomal, mitochondrial, and complement proteins
in CON-fed mice than DHA-fed mice. Gene expression analyses with
NanoString Autoimmune Gene Expression assay revealed greater
cSiO2-triggered upregulation of genes associated with TLR activation, DNA
signaling, proinflammatory cytokines,  chemokines, type 1 and 2
IFN response signatures, lymphocyte trafficking, MHC class 1 antigen
presentation, B and T cell activation at 7 and 28 d PI in CON-fed mice
than those fed DHA. Ingenuity Pathway Analysis (IPA) further demonstrated
that DHA supplementation quelled cSiO2-induced responses top upstream
regulators of proinflammatory and IFN-regulated gene networks to observed
in CON-fed mice. Altogether, this short-term model illustrated that DHA
suppression of aberrant acute cSiO2-induced inflammation is linked to
altered regulation of autoimmune-related gene expression in lupus-prone
mice.