Role of Oxidative Stress in the Suppression of Immune Responses in Peripheral Blood Mononuclear Cells Exposed to Combustible Tobacco Product Preparation

• Published in: Inflammation Vol. 40; no. 5; pp. 1622 - 1630
• Main Authors: Arimilli, Subhashini, Schmidt, Eckhardt, Damratoski, Brad E., Prasad, G. L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-10-2017; Springer Nature B.V
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Biomedical and Life Sciences; Biomedicine; Cancer; Cells, Cultured; Cigarette smoke; Cigarette smoking; Cysteine; Cytokines; Cytokines - secretion; Cytotoxicity; DNA damage; Effector cells; Glutathione; Humans; Immune response; Immunity - drug effects; Immunology; Inflammation; Interleukin 8; Internal Medicine; Leukocytes (mononuclear); Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Original; Original Article; Oxidative stress; Oxidative Stress - immunology; Particulate matter; Pathology; Perforin; Peripheral blood mononuclear cells; Pharmacology/Toxicology; Rheumatology; Secretions; T cell receptors; T-Lymphocytes, Cytotoxic - drug effects; Tobacco; Tobacco Products - adverse effects; Toll-like receptors; Tumor necrosis factor; Tumor necrosis factor-TNF; acetylcysteine; tobacco product preparations; cytolysis; cytokines; PBMCs; LPS; cytotoxicity; N-acetylcysteine
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-017-0602-9

Cigarette smoking is a major risk factor for several human diseases. Chronic inflammation, resulting from increased oxidative stress, has been suggested as a mechanism that contributes to the increased susceptibility of smokers to cancer and microbial infections. We have previously shown that whole-smoke conditioned medium (WS-CM) and total particulate matter (TPM) prepared from Kentucky 3R4F reference cigarettes [collectively called as combustible tobacco product preparations (TPPs)] potently suppressed agonist-stimulated cytokine secretion and target cell killing in peripheral blood mononuclear cells (PBMCs). Here we have investigated the role of oxidative stress from TPPs, which alters inflammatory responses
in vitro
. Particularly, we investigated the mechanisms of WS-CM-induced suppression of select cytokine secretions in Toll-like receptor (TLR) agonist-stimulated cells and target cell killing by effector cells in PBMCs. Pretreatment with
N
-acetyl cysteine (NAC), a precursor of reduced glutathione and an established anti-oxidant, protected against DNA damage and cytotoxicity caused by exposure to WS-CM. Similarly, secretion of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 in response to TLR-4 stimulation was restored by pretreatment with NAC. Target cell killing, a functional measure of cytolytic cells in PBMCs, is suppressed by WS-CM. Pretreatment with NAC restored the target cell killing in WS-CM treated PBMCs. This was accompanied by higher perforin levels in the effector cell populations. Collectively, these data suggest that reducing oxidative stress caused by cigarette smoke components restores select immune responses in this
ex vivo
model.