Interleukin-10 expression is positively correlated with oxidized LDL deposition and inversely with T-lymphocyte infiltration in atherosclerotic intimas of human coronary arteries
The inflammatory balance modulated by pro- and anti-inflammatory cytokines in atherosclerotic lesions is still unclear. The purpose of this study was to investigate the immunohistochemical localization of interleukin-10 (IL-10) and the topographical correlation between IL-10-positive cells and the other inflammatory cells in human coronary arteries. Coronary arteries (242 sections) were obtained from 43 Japanese patients (mean age: 72+/-14 years) at autopsy, and the intimal changes were classified according to the classification of the American Heart Association. The immunohistochemical distributions of IL-10, oxidized low-density lipoprotein (oxLDL), macrophages, and lymphocytes were examined morphometrically. We compared the ratios of IL-10-positive cells/macrophages and T-lymphocyte number among the shoulder and in other areas of type IV lesions and in atherosclerotic lesion types. IL-10 was expressed mainly by macrophages, and the positive cell number increased as the lesions became advanced (p<0.0001). The number of IL-10-positive cells was positively correlated with that of oxLDL-positive cells, and inversely with infiltrating T-lymphocytes (p<0.01). IL-10 expression in type IV-plaque shoulder was significantly lower than that in fibrous cap and the deeper portion under necrotic core (p<0.01). These findings suggest that IL-10 expression, seen mainly in macrophages, was possibly upregulated with oxLDL, and was inversely correlated with T-lymphocytic function in atherosclerotic coronary intimas.
Available from: Makoto Sonobe
- "A standard two-step technique was implemented, using polymeric conjugates as secondary antibodies for MUC5B and MUC5AC , and the standard avidin–biotin–peroxidase complex technique was used to detect TTF-1. Primary anti-mucin antibodies were as follows: anti-MUC5B (H-300, Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) and anti-MUC5AC (CLH2, Novocastra, New Castle Upon Tyne, UK). "
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The characteristics of non-terminal respiratory unit (TRU) type lung adenocarcinoma are still unclear. The aim of the present study was to characterize non-TRU type lung adenocarcinoma.
Materials and Methods
We analyzed the expression of mucins MUC5B and MUC5AC, as well as thyroid transcription factor-1 (TTF-1), using a tissue microarray comprising lung adenocarcinoma specimens from 244 consecutive patients. The presence of mutations in EGFR and KRAS were also determined.
TTF-1, MUC5B, and MUC5AC were detected in 219 (89.8%), 75 (30.7%), and 33 cases (13.5%), respectively. Cluster analysis of protein expression profiles and EGFR and KRAS mutations yielded five groups of tumors as follows: TRU1-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(-)]; TRU2-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(+)]; Combined-type [TTF-1(+), MUC5B(+), and/or MUC5AC(+)]; Bronchiolar-type [TTF-1(-), MUC5B(+) and/or MUC5AC(+)]; and Null-type [TTF-1(-), MUC5B(-), MUC5AC(-), EGFR mutations(-), KRAS mutations(-)]. TRU-type tumors, which include TRU1- and TRU2-type tumors, were significantly associated with TRU morphology, whereas Bronchiolar-type tumors were associated with non-TRU morphology. Combined-type cases exhibited intermediate morphologies between TRU-type and Bronchiolar-type cases. TRU-type was associated with significantly better prognosis, followed by Combined-type, Bronchiolar-type, and Null-type (disease-free survival [DFS] P = 0.017; overall survival [OS], P = 0.002). Multivariate analyses indicated that non-TRU type tumors, which include Bronchiolar-, Combined-, Null-type tumors, were significantly correlated with poorer prognoses for DFS (hazard ratio = 1.785; 95% CI, 1.041–3.063; P = 0.035) and OS (hazard ratio = 1.928; 95% CI, 1.084–3.421; P = 0.025).
This study revealed three distinct subtypes of non-TRU type adenocarcinomas. Additionally, non-TRU type tumors were associated with worse prognoses than TRU type tumors. The results presented here may be useful for select patients should appropriate therapies become available
Available from: eurheartj.oxfordjournals.org
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ABSTRACT: The present study investigates the expression and localization of interleukin (IL)-10, an important anti-inflammatory cytokine, in atherectomy specimens from patients with stable and unstable angina.
Twenty-two patients with stable angina and 21 with unstable angina who underwent directional coronary atherectomy for de novo lesions were studied. The atherectomy specimens were morphologically assessed and immunohistochemically stained with antibodies for IL-10, macrophages, smooth muscle cells, and endothelial cells. The localization and immunopositive areas were evaluated using an image analysing system. Immunoreactivity for IL-10 was detected in coronary plaques, especially in macrophages. Immunopositive areas of macrophages and IL-10, as well as the incidence of thrombus formation, were significantly greater in specimens from patients with unstable angina than in those from patients with stable angina (macrophages, P<0.001; IL-10, P<0.05; thrombus formation, P<0.05; respectively). Even after adjustment, IL-10 expression and the incidence of thrombus formation were significantly greater in the unstable angina group (P<0.05, each). The immunoreactivities for smooth muscle cells and endothelial cells did not differ between the two groups.
IL-10 was more frequently expressed in specimens from patients with unstable angina. This finding might contribute to a better understanding of plaque instability.
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ABSTRACT: Few studies regarding the topographical expression of heme oxygenase-1 (HO-1) and its pathophysiological role in human coronary atherosclerotic lesions, particularly in relation to type 2 diabetes mellitus (DM) and intimal angiogenesis, have been reported. HO-1 expression was immunohistochemically examined in 312 tissue blocks of coronary arteries obtained from 53 Japanese autopsy cases in Hisayama cohort study that included 19 diabetic subjects and 34 age- and sex-matched non-diabetic subjects (56-93 years old, mean+/-S.D.: 73+/-10). The HO-1 was ubiquitously distributed in atherosclerotic intima, and was mainly expressed by macrophages and endothelial cells, and partly by smooth muscle cells. The prevalence of HO-1 expression increased as the lesion type (as classified by the American Heart Association (AHA) Committee) and stenotic grade progressed (p<0.0001), and was significantly higher in diabetic than in non-diabetic subjects (p<0.01). This HO-1 overexpression was associated with greater CD-68-positive macrophage infiltration (p=0.005). Interestingly, the distribution of HO-1-positive cells was accentuated in coronary atherosclerotic lesions with intimal microvessels in diabetic subjects (p<0.05), particularly those with hypercholesterolemia (p<0.05), and was preferentially distributed in the shoulder region of atherosclerotic lesion type IV in the AHA classification (p<0.01). In conclusion, HO-1 expression was distributed in overall human coronary atherosclerotic lesions, particularly in diabetic subjects, indicating that HO-1 expression is intimately associated with atherogenesis and may play an important role as an adaptive molecule in the inflammatory-repair process. The association of HO-1 overexpression with a greater extent of intraplaque angiogenesis suggests a multi-faceted role for HO-1 in modulating the progression of atherosclerosis.
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