Interleukin-10 expression is positively correlated with oxidized LDL deposition and inversely with T-lymphocyte infiltration in atherosclerotic intimas of human coronary arteries

Showa University, Shinagawa, Tōkyō, Japan
Pathology - Research and Practice (Impact Factor: 1.4). 03/2006; 202(3):141-50. DOI: 10.1016/j.prp.2005.12.005
Source: PubMed


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.

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    • "A standard two-step technique was implemented, using polymeric conjugates as secondary antibodies for MUC5B and MUC5AC [16], 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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    ABSTRACT: Objectives 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. Results 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). Conclusion 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
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