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We previously demonstrated that the most bioactive vitamin A metabolite, all-trans retinoic acid (ATRA), increased T helper 2-associated responses induced in pigs by infection with the parasitic nematode Ascaris suum We also showed that ATRA potentiated the mRNA expression of several IL-4 induced chemokines (chemokine (CC motif) ligand 11 [(CCL11), CCL17, CCL22 and CCL26] associated with alternative activation (M2a) in porcine macrophages in vitro. Herein, several mechanisms whereby ATRA affects IL-4 signaling are profiled using large-scale real time PCR and RNA-Seq analysis. Twenty-three genes associated with M2a markers in other species were independently upregulated by both IL-4 and ATRA, including the adenosine receptor A2B (ADORA2B), cysteinyl leukotriene receptor 2 (CYSLTR2) and the vitamin D receptor (VDR). ATRA synergistically enhanced IL-4 up-regulation of Hepatitis A virus cellular receptor 2 (HAVCR2) and transglutaminase 2 (TGM2) and further repressed IL-4 down-regulated CD163 and Cytochrome b-245, beta polypeptide (CYBB) mRNA. Macrophages treated with ATRA exhibited a dose-dependent reduction in phagocytosis of opsonized Staphylococcus aureus. In addition, the combination of IL-4 and ATRA up-regulated the anti-inflammatory protein, IL-1R antagonist (IL1RN) and TGM2. These data indicate that ATRA induces a state of partial alternative activation in porcine macrophages, and amplifies certain aspects of M2a activation induced by IL-4. Given the prevalence of allergic and parasitic diseases worldwide and the close similarities in the porcine and human immune responses, these findings have important implications for the nutritional regulation of allergic inflammation at mucosal surfaces.
This article was published in the following journal.
Name: Developmental and comparative immunology
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Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.
A cytochrome P450 enzyme that resides in the ENDOPLASMIC RETICULUM. It catalyzes the conversion of trans-RETINOIC ACID to 4-hydroxyretinoic acid.
A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signalling pathways.
A cytochrome P450 enzyme family whose members function in the metabolism of RETINOIC ACID. It includes RETINOIC ACID 4-HYDROXYLASE.
The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.
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