Effects of tobacco smoke on IL-16 in CD8<sup>+</sup> cells from human airways and blood: a key role for oxygen free radicals?

Andersson, Anders; Bossios, Apostolos; Malmhäll, Carina; Sjöstrand, Margareta; Eldh, Maria; Eldh, Britt-Marie; Glader, Pernilla; Åndersson, Bengt; Qvarfordt, Ingemar; Riise, Gerdt C.; Lindén, Anders

doi:10.1152/ajplung.00387.2009

Cited by 7 publications

(16 citation statements)

References 43 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Still, one mechanism is smoking-induced increased lipid-oxidation (80) and closely related to this, oxidative stress (81). Smoking is associated with systemic and local inflammation with raised levels of pro-inflammatory cytokines and cells, in particular in chronic obstructive pulmonary disease (82), which could play a role also in atherosclerosis.…”

Section: Diabetes and Causes Of Immune Activation In Atherosclerosismentioning

confidence: 99%

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Frostegård

2013

Front. Endocrinol.

View full text Add to dashboard Cite

Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1β (IL-1β), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglycemia and oxidative stress appear to accelerate the development of atherosclerosis, one mechanism could be via promotion of immune reactions. To prove that immune reactions are causative of atherosclerosis and CVD, further studies with immune-modulatory treatments are needed.

show abstract

Section: Diabetes and Causes Of Immune Activation In Atherosclerosismentioning

confidence: 99%

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Frostegård

2013

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…The water-soluble components of tobacco smoke were generated in the form of cigarette smoke extract (CSE) as described in detail previously. 19 , 20 Briefly, CSE was generated by leading mainstream smoke from ten medium nicotine and tar commercial cigarettes (Marlboro™, Philip Morris Int, Richmond, VA, USA) through 15 mL of cell culture medium (HyClone RPMI1640 Media, GE Healthcare Bio-Sciences AB) by vacuum suction at room temperature. The burning time for each cigarette was 3 minutes.…”

Section: Methodsmentioning

confidence: 99%

“…The enriched NK cells were cultured with or without CSE (dilution 1:25) and with or without an OFR scavenger (L-glutathione, 10 −2 M) in complete medium (ie, cell culture media, supplemented with fetal calf serum [FCS: 10%] [both from Sigma-Aldrich, St Louis, MO, USA], L-glutamine [4 mmol/mL], and penicillin/streptomycin [100 units/100 μg/mL] [HyClone] as previously described 19 , 20 ). The utilized concentration of L-glutathione (10 −2 M) was chosen based on its effect on IL-16 in a previous study.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously demonstrated that tobacco smoke does affect the production and release of IL-16 from human T-cells in the airways in vivo and in isolated cells in vitro. 18 – 20 Specifically, it seems as if tobacco smoke depletes IL-16 from local CD8 + T-cells in the airways. 20 Moreover, we have shown that long-term exposure to tobacco smoke alters IL-16 protein in palatine tonsils, which is compatible with systemic effects.…”

Section: Introductionmentioning

confidence: 99%

“… 18 – 20 Specifically, it seems as if tobacco smoke depletes IL-16 from local CD8 + T-cells in the airways. 20 Moreover, we have shown that long-term exposure to tobacco smoke alters IL-16 protein in palatine tonsils, which is compatible with systemic effects. 19 For the current study, we hypothesized that long-term exposure to tobacco smoke alters the biology of IL-16 at the systemic level by exerting effects on circulating blood leukocytes, including NK cells, CD8 + and CD4 + T-cells, B-cells, and monocytes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD

Andersson¹,

Malmhäll²,

Houltz³

et al. 2016

COPD

Self Cite

View full text Add to dashboard Cite

BackgroundLong-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8+) and helper (CD4+) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4+-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR).MethodsWe quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein.ResultsThe extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4+ T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug.ConclusionLong-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors – conditions that are overrepresented among smokers.

show abstract

The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers

et al. 2018

Self Cite

View full text Add to dashboard Cite

Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM), the exposure to water-soluble tobacco smoke components (WTC) enhanced gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex () and a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 caused a concentration-dependent increase in the gene expression of and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.

show abstract

Effects of tobacco smoke on IL-16 in CD8⁺ cells from human airways and blood: a key role for oxygen free radicals?

Cited by 7 publications

References 43 publications

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD

The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers

Contact Info

Product

Resources

About

Effects of tobacco smoke on IL-16 in CD8+ cells from human airways and blood: a key role for oxygen free radicals?

Cited by 7 publications

References 43 publications

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Immune Mechanisms in Atherosclerosis, Especially in Diabetes Type 2

Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD

The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers

Contact Info

Product

Resources

About

Effects of tobacco smoke on IL-16 in CD8⁺ cells from human airways and blood: a key role for oxygen free radicals?