D-Lactate Increases Cytokine Production in Bovine Fibroblast-Like Synoviocytes via MCT1 Uptake and the MAPK, PI3K/Akt, and NFκB Pathways

SIMPLE SUMMARY: Lameness is commonly observed in dairy cattle, affecting animal welfare and farm production. Ruminal acidosis is a metabolic disorder that frequently has been associated with lameness. Has been observed that during acute ruminal acidosis increase the presence of D-lactate in synovial fluid and induces the appearance of a joint inflammation, characterized by an aseptic synovitis. The fibroblast-like synoviocytes is one the main synovium cells involved in the onset of joint inflammation. The aim of this study was to assess the proinflammatory effect of D-lactate on bovine fibroblast-like synoviocytes. We demonstrated that D-lactate increase the release of proinflammatory cytokines, activating intracellular signaling pathways in bovine synoviocytes. Our results support the role of D-lactate in the onset of synovitis and lameness in cattle. ABSTRACT: Acute ruminal acidosis (ARA) is caused by the excessive intake of highly fermentable carbohydrates, followed by the massive production of D-lactate and the appearance of neutrophilic aseptic polysynovitis. Bovines with ARA develop different lesions, such as ruminitis, polioencephalomalacia (calves), liver abscess and lameness. Lameness in cattle with ARA is closely associated with the presence of laminitis and polysynovitis. However, despite decades of research in bovine lameness as consequence of ruminal acidosis, the aetiology and pathogenesis remain unclear. Fibroblast-like synoviocytes (FLSs) are components of synovial tissue, and under pathological conditions, FLSs increase cytokine production, aggravating inflammatory responses. We hypothesized that D-lactate could induce cytokine production in bovine FLSs. Analysis by qRT-PCR and ELISA revealed that D-lactate, but not L-lactate, increased the expression of IL-6 and IL-8 in a monocarboxylate transporter-1-dependent manner. In addition, we observed that the inhibition of the p38, ERK1/2, PI3K/Akt, and NF-κB pathways reduced the production of IL-8 and IL-6. In conclusion, our results suggest that D-lactate induces an inflammatory response; this study contributes to the literature by revealing a potential key role of D-lactate in the polysynovitis of cattle with ARA.