Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease

<p>Mucosal-associated invariant T (MAIT) cells have been reported to play an important role in mucosal immunity. However, little is known about the roles of MAIT cells in chronic obstructive pulmonary disease (COPD). The aims of this study were to examine the levels of circulating MAIT cells and their subsets in COPD patients and to investigate the potential relationship between clinical parameters and MAIT cell levels. Forty-five COPD patients and 57 healthy control subjects were enrolled in the study. Circulating MAIT cells and their subset levels in the peripheral blood were measured by flow cytometry. Disease grades were classified according to the GOLD criteria for the assessment of severity of COPD. Circulating MAIT cell levels were found to be significantly reduced in COPD patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets. Interestingly, elevated serum C-reactive protein level and reduced FEV₁/FVC ratio were associated with MAIT cell deficiency in COPD patients. Furthermore, the circulating MAIT levels were found to be significantly lower in patients with moderate to severe COPD than in patients with mild COPD. Our data shows that MAIT cells are numerically deficient in the peripheral blood of patients with COPD. In addition, this MAIT cell deficiency was found to reflect inflammatory activity and disease severity. These findings provide important information for monitoring the changes in MAIT cell levels and for predicting the prognosis during the disease course.</p

MS-275 and RGFP966 reduced arterial wall thickness in angiotensin II-induced hypertensive mice by suppressing E2F3 and GATA6 expression.

(A) Representative images of H&E stained aortas from sham, angiotensin II group (Ang II), MS-275-treated angiotensin II group (Ang II + MS-275), and RGFP966-treated angiotensin II group (Ang II + RGFP966). Scale bar = 100 μm. (B) Arterial wall thickness was quantified. Data are means ± SE (n = 7/group). ***p ## p ### p # p < 0.05 versus angiotensin II group; NS, not significant.</p

IC₅₀ [μM] values for TMP269, RGFP966, and TSA.

IC50 [μM] values for TMP269, RGFP966, and TSA.</p

Piceatannol attenuates phosphorylated p38 MAPK expression in the UUO kidney.

<p>(A) Kidney lysates were used for western blot analysis. Antibodies against p-JNK2 (Thr183/Tyr185), JNK2, p-ERK1 (Thr202/Tyr204), ERK1, p-p38 (Thr180/Tyr182), and p38 were used. GAPDH was used as a loading control. (B-E) Quantification analysis was performed using densitometry. The data are expressed as the means ± SD of the mice (n = 6 per group). *<i>P</i><0.05, **<i>P</i><0.01, and ***<i>P</i><0.001 compared with the contralateral kidney. ^#<i>P</i> <0.05 compared with the UUO kidney. NS indicates not significant compared with the UUO kidney.</p

MS-275 and RGFP966 reduced cardiac hypertrophy in angiotensin II-induced hypertensive mice.

(A) The HW/BW ratio was analyzed 2 weeks after Ang II infusion (n = 8 per group). ***p #p #p ###p < 0.001 versus angiotensin II group.</p

MS-275 reduced inflammation in angiotensin (Ang) II-induced hypertensive mice.

The transcript levels of iNOS (A), TNF-α (B), IL-1β (C), MCP-1 (D), VCAM-1 (E), and ICAM-1 (F) were determined using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in aortas of sham and Ang II-induced mice treated with vehicle, MS-275, or RGFP966. Results are means ± SE (n = 8 per group). * p # p ## p < 0.01 versus angiotensin II group; NS, not significant. (G) Representative aortic images for macrophage infiltration are shown. Scale bar = 50 μm.</p

MS-275 and RGFP966 did not reduce oxidases and restore antioxidant enzymes in angiotensin (Ang) II-induced hypertensive mice.

The transcript levels of Nox1 (A), Nox2 (B), Nox4 (C), p22phox (D), p47phox (E), Cox-2 (F), and SOD3 (G) were determined using qRT-PCR in aortas of sham and Ang II-induced mice treated with vehicle, MS-275, or RGFP966. Results are ± SE (n = 8 per group). * p < 0.05 and ** p < 0.01 versus sham group; NS, not significant.</p

MS-275 and RGFP966 reduced systolic blood pressure in angiotensin II-induced hypertensive mice by downregulating AT1 and angiotensin-converting enzyme 1 (ACE1) expression.

(A) After angiotensin II infusion (1.3 mg·kg-1·day-1) to mice for 1 week, we injected MS-275 or RGFP966 (both 3 mg·kg-1·day-1) daily to mice for additional 7 days. Systolic blood pressures were measured in awake mice. (B and C) Transcript levels of aortic AT1 and ACE1 were quantified using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). GAPDH was used to normalize the values. Data are presented as the means ± SE (n = 8 per group). ***p #p ###p < 0.001 versus angiotensin II group; NS, not significant.</p

Piceatannol attenuates the expression of UUO-induced renal HDAC5/HDAC6 protein.

<p>(A) Kidney lysates were used for western blot analysis. Antibodies against HDAC4, HDAC5, HDAC6, and HDAC10 were used. GAPDH was used as a loading control. (B-E) Quantification analysis was performed using densitometry. The data are expressed as the means ± SD of the mice (n = 6 per group). *<i>P</i><0.05 and ***<i>P</i><0.001 compared with the contralateral kidney. ^###<i>P</i> <0.001 compared with the UUO kidney. NS indicates not significant compared with the UUO kidney.</p

Primers for reverse transcription-polymerase chain reaction (RT-PCR).

Primers for reverse transcription-polymerase chain reaction (RT-PCR).</p