Microcystin-leucine arginine (MC-LR) induced inflammatory response in bovine sertoli cell via TLR4/NF-kB signaling pathway

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

“…Accumulating studies have indicated that various signaling pathways in SCs are implicated with spermatogenesis 27,28 . Until now, numerous signaling pathways have been found in Sertoli cells, including the androgensignaling pathway 29,30 , the AMP-activated protein kinase (AMPK) signaling pathway 31 , the follicle stimulating hormone (FSH)/adenylate cyclase/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway 32 , the Hippo signaling pathway 33,34 , the intergrin mediated signaling pathway 4,35 , the Janus kinase/signal transducer and activator of transcription signaling pathway 36,37 , the mitogen-activated protein kinases (MAPK) signaling pathway [38][39][40][41][42][43][44] , the nuclear factor kappa B signaling pathway 45,46 , the nitric oxide/soluble guanylyl cyclase/cyclic guanosine monophosphate/ protein kinase G signaling pathway 47,48 , the Notch signaling pathway 49 , the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3k)/AKT serine/threonine kinase (Akt) signaling pathway 50,51 , the Sonic Hedgehog signaling pathway 52,53 , the transforming growth factor-β (TGF-β)/ Smad signaling pathway 54 , and the Wnt signaling pathway 55,56 (Table 1). Among all these signaling pathways, the TGF-β/Smad, AMPK, and MAPK signaling pathways have attracted much more attentions in the past decade.…”

Pharmacological inhibition of TLR4/NF‐κB with TLR4‐IN‐C34 attenuated microcystin‐leucine arginine toxicity in bovine Sertoli cells

“…Based on these data we decided to use 10 μ m of C34 for the main experiment. Similarly, the viability of bovine Sertoli cells exposed to varying concentrations of MC‐LR reported in our earlier study (Adegoke, Wang, Machebe, Wang, et al, ) and preliminary experiment showed that the highest toxic concentration of MC‐LR at which bovine Sertoli can survive is 80 μg/L but cannot survive at 100 μg/L concentration of MC‐LR (Figure S2); therefore, we decided to use 80 μg/L.…”

“…Previous studies on MC‐LR (Adamovsky et al, ; Adegoke, Wang, Machebe, Adeniran, et al, ; Adegoke, Wang, Machebe, Wang, et al, ) indicated that MC‐LR elicit its toxic effects via TLR4 signaling pathways. Therefore, the TLR4 signaling pathway was made the target for amelioration and attenuation of MC‐LR toxicity in this study.…”

“…Recent studies have also revealed that Sertoli cells express TLRs particularly TLR4, which help to recognize a wide range of bacterial infections and toxins (Adegoke et al, ; Starace et al, ; Winnall, Muir, & Hedger, ; Wu et al, ), but also play a vital role in the induction of the inflammatory response. According to Huggins et al (), the TLRs, including TLR4, have been shown to play a crucial role in inflammatory diseases.…”

“…According to Huggins et al (), the TLRs, including TLR4, have been shown to play a crucial role in inflammatory diseases. MC‐LR has been reported to induce inflammation in bovine Sertoli cells (Adegoke, Wang, Machebe, Wang, et al, ), in human umbilical vein endothelial cells (Shi, Zhou, & Zhang, ) and activates TLRs, particularly TLR4 in the RAW 264.7 cell line (Adamovsky et al, ). Meanwhile, all TLR signaling pathways culminate in activation of the transcription factor nuclear factor‐kappaB (NF‐κB), which controls the expression of an array of inflammatory cytokine genes (Taro & Shizuo, ).…”