Calcitriol modulate post-ischemic TLR signaling pathway in ischemic stroke patients

Background: Neuroinflammation is a significant contributor to post-ischemic neuronal death after stroke, and Toll-Like Receptors (TLRs) are one of the essential mediators in many inflammatory pathways. TLRs activate the nuclear factor kappa beta (NF-k beta), which promotes the expression of various pro-inflammatory genes such as interleukin (IL-1 beta) and IL-6. 1,25(OH)2D3, also known as calcitriol, is an active form of vitamin D3 that acts as a neurosteroid compound with anti-inflammatory properties. This study aimed to determine the modulatory effects of calcitriol hormone on post-ischemic immunity response.Methods: Neurological tests and conventional blood factors were evaluated in patients with stroke symptoms upon arrival (n = 38) to confirm the stroke. A blood sample was taken from each stroke patient immediately upon admission and again after 24 h. The experimental group was given 10 mu g calcitriol orally. The gene expression levels of TLR4, TLR2, NF-k beta, IL-1 beta, and IL-6 pro-inflammatory factors were measured using real-time PCR. The protein expression of TLR4 and NF-k beta markers was assessed using the flow cytometry technique.Results: TLR4, NF-k beta, and pro-inflammatory factors IL-1 beta and IL-6 expression increased significantly after an ischemic stroke, and calcitriol could modulate the TLR4/NF-k beta signaling pathway 24 h after ischemia.Conclusions: Calcitriol may be considered a protective reagent after ischemia by reducing the TLR4/NF-kB activation cascade and probably plays a beneficial role in reducing and improving ischemic stroke patients' symptoms. Trial registration: Iranian Registry of ClinicalTrials identifier: IRCT2017012532174N1.