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

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 β (NF-kβ), which promotes the expression of various pro-inflammatory genes such as interleukin (IL-1β) 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.

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 μg calcitriol orally. The gene expression levels of TLR4, TLR2, NF-kβ, IL-1β, and IL-6 pro-inflammatory factors were measured using real-time PCR. The protein expression of TLR4 and NF-kβ markers was assessed using the flow cytometry technique.

TLR4, NF-kβ, and pro-inflammatory factors IL-1β and IL-6 expression increased significantly after an ischemic stroke, and calcitriol could modulate the TLR4/NF-kβ signaling pathway 24 h after ischemia.

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.

Iranian Registry of Clinical Trials identifier: IRCT2017012532174N1.