Increased adipose tissue expression of proinflammatory CD40, MKK4 and JNK in patients with very severe chronic obstructive pulmonary disease.
BACKGROUND
CD40, a transmembrane receptor of the tumor necrosis factor gene superfamily, is activated in response to cellular stress, including hypoxia, and orchestrates the process of inflammation via secondary messengers such as mitogen-activated protein kinase kinase 4 (MKK4) and c-Jun NH(2)-terminal kinases (JNK).


OBJECTIVE
We hypothesized that CD40, MKK4 and JNK expression is increased in the adipose tissue of patients with very severe chronic obstructive pulmonary disease (COPD).


METHODS
In 20 patients with stable COPD, lung function was assessed using body plethysmography, and samples of subcutaneous adipose tissue were analyzed using real-time PCR. Body composition, including fat mass index (FMI), was assessed by bioelectrical impedance.


RESULTS
12 patients in GOLD stage I-III (age 61.6 ± 8.6 years, 4 females, mean partial pressure of oxygen in arterial blood, PaO(2), 9.38 ± 0.21 kPa) were compared to 8 patients in GOLD stage IV (age 62.6 ± 6.3 years, all male, mean PaO(2) 7.70 ± 0.37 kPa). Compared to patients in GOLD stage I-III, patients in GOLD stage IV had lower FMI (p = 0.004), being associated with significantly higher adipose tissue expression of CD40, MKK4 and JNK [ΔΔCt: 2.55 (1.99, 4.40) vs. 1.87 (1.63, 2.23), p = 0.013; 5.19 (3.13, 5.96) vs. 2.98 (2.82, 3.86), p = 0.002; 9.01 (5.12, 11.41) vs. 4.65 (4.42, 6.26), p = 0.001, respectively]. Log-transformed CD40, MKK4 and JNK expression was significantly inversely related to PaO(2), respectively.


CONCLUSIONS
Upregulation of proinflammatory CD40, MKK4 and JNK gene expression in adipose tissue in very severe COPD raises the possibility of a role of chronic systemic hypoxia in the pathogenesis of adipose tissue inflammation in COPD.
Tkacova
Ruzena
R
Department of Respiratory Medicine, Faculty of Medicine, P.J. Safarik University and L. Pasteur Teaching Hospital, Kosice, Slovakia. ruzena.tkacova@upjs.sk
Ukropec
Jozef
J
Skyba
Peter
P
Ukropcova
Barbara
B
Pobeha
Pavol
P
Kurdiova
Timea
T
Joppa
Pavol
P
Klimes
Iwar
I
Tkac
Ivan
I
Gasperikova
Daniela
D
D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism*; D001823:Body Composition; D019013:CD40 Antigens / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive; D015854:Up-Regulation / Q000502:physiology
D019013:CD40 Antigens; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human