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CBD Attenuates Hyperglycemia Induced Pro-Inflammatory Cytokines, Chemokines and M1 Polarization in THP1 monocytes

Chandrakala Aluganti Narasimhulu
University of Central Florida

Co-Authors: Karina Villalba1, Dinender K. Singla1
1University of Central Florida

Hyperglycemia is well established as a potent stimulator of monocyte activity which is a major event in the pathogenesis of various diseases including atherosclerosis, diabetes, cancer, and neurological diseases. Cannabidiol (CBD), the most abundant non-psychotropic cannabinoid found in Cannabis sativa L. is well known for its anti-inflammatory properties; however, the mechanisms of anti-inflammatory properties of CBD are obscure. Therefore, we investigated the mechanisms of anti-inflammatory properties of CBD attenuates under hyperglycemic conditions of monocyte infiltrations.
Hypothesis: We hypothesize that CBD attenuates the hyperglycemia in monocytes as well as provide anti-inflammatory properties via enhancing M2 macrophages

THP-1 cells were divided into 3 groups: Control, Glucose and Glucose+CBD. Cells were incubated with glucose (50mM) for 24 hrs, followed by with CBD (20 µg/ml) for additional 24hrs. After 48hrs incubation cells were harvested and used for immunocytochemistry (ICC), and RNA isolation followed by RT-PCR. Glucose induced monocyte differentiation either in the presence or absence of CBD was established by analyzing M1 (iNOS) and M2 (CD206, and Arginase-1) macrophage markers. Additionally, Cytokine array (62 cytokines) was performed for all the three groups to evaluate inflammatory cytokine profile. Further, Pro-inflammatory cytokines TNFα and IL-6 were analyzed by ELISA.

A significant (p<0.05) increase in the M1 macrophage markers and pro-inflammatory markers were observed in Glucose treated cells, whereas CBD treatment significantly polarized monocytes to M2 macrophages and attenuated glucose-induced inflammation. Further a significant (p<0.05) increase in M2 macrophage markers CD206 and Arginase were observed. Hyperglycemia upregulated the expression of 43-pro-inflammatory cytokines (~1.2 to 7-fold) that are involved in inflammation, apoptosis, angiogenesis, macrophage inflammatory proteins, growth factors and adhesion molecules as compared to control, whereas CBD treatment reduced differentially the pro-inflammatory cytokine expression.

We suggest that CBD has a greater therapeutic potential in diabetic conditions by decreasing pro-inflammatory monocytes, macrophages, and cytokines. We also provide evidence that CBD enhances anti-inflammatory M2 macrophages.

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