Regulation of TLR signaling pathways by microRNAs: implications in inflammatory diseases.

The control of the immune response during the development of some diseases is crucial for the maintenance or restoration of homeostasis. Several mechanisms can initiate inflammation, one of which is the activation of toll-like receptors (TLRs), necessary to initiate the immune response to eliminate an infection. However, inappropriate activation can compromise immunological homeostasis, leading to pathologies such as autoimmune diseases, chronic inflammation, and even cancer. Regulatory mechanisms that intervene in the initiation or modulation of inflammation include microRNAs (miRNAs), which have emerged as key post-transcriptional regulators of proteins involved in distinct cellular processes, such as regulation of the immune response. The focus of this review is on the diverse roles of miRNAs in the regulation of TLR-signaling pathways by targeting multiple molecules, including TLRs, the signaling proteins and cytokines induced by TLRs. It will also address the relationships of these molecules with some diseases that involve inflammation such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), cancer, as well as bacterial or viral infections.

Hypoxia drives apoptosis independently of p53 and metallothionein transcript levels in hemocytes of the whiteleg shrimp Litopenaeus vannamei.

The cellular mechanisms used by the shrimp Litopenaeus vannamei to respond to hypoxia have been studied from the energetic metabolism and antioxidant angles. We herein investigated the participation of p53 and metallothionein (MT) in the apoptotic process in response to hypoxia in shrimp hemocytes. The Lvp53 or LvMT genes were efficiently silenced by injection of double stranded RNA for p53 or MT. The effects of silencing on apoptosis were measured as caspase-3 activity and flow cytometry in hemocytes after 24 and 48 h of hypoxia (1.5 mg DO L(-1)). Hemocytes from unsilenced animals had significantly higher apoptosis levels upon both times of hypoxia. The apoptotic levels were diminished but not suppressed in dsp53-silenced but not dsMT-silenced hemocytes after 24 h of hypoxia, indicating a contribution of Lvp53 to apoptosis. Apoptosis in normoxia was significantly higher in dsp53-and dsMT-silenced animals compared to the unsilenced controls, pointing to a possible cytoprotective role of LvMT and Lvp53 during the basal apoptotic program in normoxia. Overall, these results indicate that hypoxia augments apoptosis in shrimp hemocytes and high mRNA levels of Lvp53 and LvMT are not necessary for this response.