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Lupus-like oral mucosal lesions in mercury-induced autoimmune response in Brown Norway rats.

Seno K, Ohno J, Ota N, Hirofuji T, Taniguchi K - BMC Immunol. (2013)

Bottom Line: Dense infiltration of DC and macrophages was observed in the basement membrane (BM) zone of the oral epithelium.A linear and continuous smooth pattern of fluorescence was observed in the oral epithelial BM in addition to renal glomeruli, indicating immune complex deposits.Local autoimmune responses are involved in the pathogenesis of mercury-induced lupus-like lesions of the oral mucosa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Morphological Biology, Division of Pathology, Fukuoka Dental College, 2-15-1 Tamura, Fukuoka, Japan. johno@college.fdcnet.ac.jp.

ABSTRACT

Background: Administration of mercury at nontoxic doses induces systemic autoimmune disease in Brown Norway (BN) rats. The pathogenesis of lupus-like oral mucosal lesion by mercury-induced autoimmunity is still unclear, even though the oral mucosa is observed to be commonly affected in mercury-treated BN rats. In this study, we investigated the immunopathology of lupus-like oral mucosal lesions in a model of mercury-induced systemic autoimmunity.

Methods: Brown Norway male rats were injected subcutaneously with either phosphate-buffered saline (control) or mercury at a dose of 1.0 mg per kilogram of body weight on days 0, 3, 5, and 7. Blood, kidney, and tongue samples were taken at various timepoints for evaluation by immunohistochemistry, RT-PCR, and lupus band test (LBT).

Results: Oral mucosal lesions were classified according to three consecutive temporal phases on the basis of infiltration of immunocompetent cells as follows: (phase I) infiltration of MHC class II+ dendritic cells (DC) and macrophages; (phase II) addition of ED1+ macrophage infiltrates; and (phase III) focal infiltration of pan T cells following increased infiltration of DC and macrophages. Dense infiltration of DC and macrophages was observed in the basement membrane (BM) zone of the oral epithelium. Tissue expression of IL-4 mRNA was detected in early lesions (phase I), suggesting that locally produced IL-4 may be responsible for Th2-mediated immune response. A linear and continuous smooth pattern of fluorescence was observed in the oral epithelial BM in addition to renal glomeruli, indicating immune complex deposits.

Conclusions: Local autoimmune responses are involved in the pathogenesis of mercury-induced lupus-like lesions of the oral mucosa.

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Tissue expression of interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA in the tongue of the mercury-treated rats by real-time reverse transcription-polymerase chain reaction (qRT-PCR). A and B: qRT-PCR analyses examine expression levels of mRNA encoding IL-4 (A) and IFN-γ (B) normalized by those of glyceraldehyde-3-phosphate dehydrogenase (G3PDH). Data represents mean ± standard error (SE) of pooled data derived from three to five independent experiments. *, significantly different at p< 0.05 compared with the control. **, significantly different at p<0.01 compared with the control. §, significantly different at p<0.05 compared with phases I and II. §§, significantly different at p<0.05 compared with control, phases I, and II. C: Agarose gel electrophoresis analysis of qRT-PCR. Ctr, control; I, phase I; II, phase II; III, phase III.
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Figure 4: Tissue expression of interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA in the tongue of the mercury-treated rats by real-time reverse transcription-polymerase chain reaction (qRT-PCR). A and B: qRT-PCR analyses examine expression levels of mRNA encoding IL-4 (A) and IFN-γ (B) normalized by those of glyceraldehyde-3-phosphate dehydrogenase (G3PDH). Data represents mean ± standard error (SE) of pooled data derived from three to five independent experiments. *, significantly different at p< 0.05 compared with the control. **, significantly different at p<0.01 compared with the control. §, significantly different at p<0.05 compared with phases I and II. §§, significantly different at p<0.05 compared with control, phases I, and II. C: Agarose gel electrophoresis analysis of qRT-PCR. Ctr, control; I, phase I; II, phase II; III, phase III.

Mentions: In the mercury-treated rats, a Th2-dominated autoimmune response is induced in target organs [17]. We therefore examined tissue expression of IL-4 (Th2) and IFN-γ (Th1) mRNA in the tongue during each phase of the study. qRT-PCR analyses indicated that expression levels of mRNA encoding IL-4 normalized by that of G3PDH increased in phases I and II by 2.6 fold and 2.9 fold when compared with their control, respectively, and reached the maximum in phase III by 8.2 fold (Figure 4A). In contrast, expression levels of IFN-γ mRNA remained unchanged until phase II, whereas those increased in phase III by 2.5 fold when compared with the control (Figure 4B). These data from qRT-PCR analyses were identical to those of agarose gel electrophoresis analyses (Figure 4C).


Lupus-like oral mucosal lesions in mercury-induced autoimmune response in Brown Norway rats.

Seno K, Ohno J, Ota N, Hirofuji T, Taniguchi K - BMC Immunol. (2013)

Tissue expression of interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA in the tongue of the mercury-treated rats by real-time reverse transcription-polymerase chain reaction (qRT-PCR). A and B: qRT-PCR analyses examine expression levels of mRNA encoding IL-4 (A) and IFN-γ (B) normalized by those of glyceraldehyde-3-phosphate dehydrogenase (G3PDH). Data represents mean ± standard error (SE) of pooled data derived from three to five independent experiments. *, significantly different at p< 0.05 compared with the control. **, significantly different at p<0.01 compared with the control. §, significantly different at p<0.05 compared with phases I and II. §§, significantly different at p<0.05 compared with control, phases I, and II. C: Agarose gel electrophoresis analysis of qRT-PCR. Ctr, control; I, phase I; II, phase II; III, phase III.
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Figure 4: Tissue expression of interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA in the tongue of the mercury-treated rats by real-time reverse transcription-polymerase chain reaction (qRT-PCR). A and B: qRT-PCR analyses examine expression levels of mRNA encoding IL-4 (A) and IFN-γ (B) normalized by those of glyceraldehyde-3-phosphate dehydrogenase (G3PDH). Data represents mean ± standard error (SE) of pooled data derived from three to five independent experiments. *, significantly different at p< 0.05 compared with the control. **, significantly different at p<0.01 compared with the control. §, significantly different at p<0.05 compared with phases I and II. §§, significantly different at p<0.05 compared with control, phases I, and II. C: Agarose gel electrophoresis analysis of qRT-PCR. Ctr, control; I, phase I; II, phase II; III, phase III.
Mentions: In the mercury-treated rats, a Th2-dominated autoimmune response is induced in target organs [17]. We therefore examined tissue expression of IL-4 (Th2) and IFN-γ (Th1) mRNA in the tongue during each phase of the study. qRT-PCR analyses indicated that expression levels of mRNA encoding IL-4 normalized by that of G3PDH increased in phases I and II by 2.6 fold and 2.9 fold when compared with their control, respectively, and reached the maximum in phase III by 8.2 fold (Figure 4A). In contrast, expression levels of IFN-γ mRNA remained unchanged until phase II, whereas those increased in phase III by 2.5 fold when compared with the control (Figure 4B). These data from qRT-PCR analyses were identical to those of agarose gel electrophoresis analyses (Figure 4C).

Bottom Line: Dense infiltration of DC and macrophages was observed in the basement membrane (BM) zone of the oral epithelium.A linear and continuous smooth pattern of fluorescence was observed in the oral epithelial BM in addition to renal glomeruli, indicating immune complex deposits.Local autoimmune responses are involved in the pathogenesis of mercury-induced lupus-like lesions of the oral mucosa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Morphological Biology, Division of Pathology, Fukuoka Dental College, 2-15-1 Tamura, Fukuoka, Japan. johno@college.fdcnet.ac.jp.

ABSTRACT

Background: Administration of mercury at nontoxic doses induces systemic autoimmune disease in Brown Norway (BN) rats. The pathogenesis of lupus-like oral mucosal lesion by mercury-induced autoimmunity is still unclear, even though the oral mucosa is observed to be commonly affected in mercury-treated BN rats. In this study, we investigated the immunopathology of lupus-like oral mucosal lesions in a model of mercury-induced systemic autoimmunity.

Methods: Brown Norway male rats were injected subcutaneously with either phosphate-buffered saline (control) or mercury at a dose of 1.0 mg per kilogram of body weight on days 0, 3, 5, and 7. Blood, kidney, and tongue samples were taken at various timepoints for evaluation by immunohistochemistry, RT-PCR, and lupus band test (LBT).

Results: Oral mucosal lesions were classified according to three consecutive temporal phases on the basis of infiltration of immunocompetent cells as follows: (phase I) infiltration of MHC class II+ dendritic cells (DC) and macrophages; (phase II) addition of ED1+ macrophage infiltrates; and (phase III) focal infiltration of pan T cells following increased infiltration of DC and macrophages. Dense infiltration of DC and macrophages was observed in the basement membrane (BM) zone of the oral epithelium. Tissue expression of IL-4 mRNA was detected in early lesions (phase I), suggesting that locally produced IL-4 may be responsible for Th2-mediated immune response. A linear and continuous smooth pattern of fluorescence was observed in the oral epithelial BM in addition to renal glomeruli, indicating immune complex deposits.

Conclusions: Local autoimmune responses are involved in the pathogenesis of mercury-induced lupus-like lesions of the oral mucosa.

Show MeSH
Related in: MedlinePlus