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Developmental expression of Toll?like receptors in the guinea pig lung.

ABSTRACT: The guinea pig is a useful model for investigating infectious and non?infectious lung diseases due to the sensitivity of its respiratory system and susceptibility to infectious agents. Toll?like receptors (TLRs) are important components of the innate immune response and are critical for lung immune function. In the present study, the differentiation of epithelial cells in the guinea pig lung was examined during gestation by studying anatomic morphology and the major epithelial cell types using cell type?specific markers. The developmental expression of all 9 TLRs and the TLR signaling adaptors myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF?6) were investigated by reverse transcription?quantitative polymerase chain reaction and western blotting analysis. The formation of lung lobes in guinea pigs was observed at 45 days of gestation (dGA), along with the expression of the basal cell marker keratin 14 and the alveolar type II cell marker pro?surfactant protein. However, the cube cell marker secretoglobin family1A member 1 and ciliated cell marker b?tubulin IV were only detected in the lungs from 52 dGA onward. The expression levels of all TLRs, MyD88 and TRAF?6 were determined in lung tissues harvested from embryos, newborn, postnatal and adult animals. The expression levels of all TLR signaling components displayed similar dynamic expression patterns with gestation age and postnatal maturation time, except for TLR?4 and TLR?7. mRNA expression levels of TLR components were significantly increased in the lungs at 45 and 52 dGA, compared with later developmental stages. These results suggest that TLR expression in the guinea pig lung is developmentally regulated, enhancing the understanding of lung biology in guinea pig models.

SUBMITTER: Ma L

PROVIDER: S-EPMC5367368 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Developmental expression of Toll‑like receptors in the guinea pig lung.

Ma Lingjie L Yang Jiali J Yang Li L Shi Juan J Xue Jing J Li Yong Y Liu Xiaoming X

Molecular medicine reports 20170117 3

The guinea pig is a useful model for investigating infectious and non‑infectious lung diseases due to the sensitivity of its respiratory system and susceptibility to infectious agents. Toll‑like receptors (TLRs) are important components of the innate immune response and are critical for lung immune function. In the present study, the differentiation of epithelial cells in the guinea pig lung was examined during gestation by studying anatomic morphology and the major epithelial cell types using c ...[more]

PMID: 28098883

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Project description:The mechanisms of diabetic renal injury remain unclear. Recent studies have shown that immunological and inflammatory elements play important roles in the initiation and development of diabetic nephropathy (DN). Toll-like receptors (TLRs) comprise a superfamily of innate immune system receptors. The roles and mechanisms of TLRs in the pathogenesis of diabetic renal lesions are mostly unknown. Compared with rodents, miniature pigs are more similar to humans with respect to metabolism, kidney structure, and immune system, and therefore represent an ideal large-animal model for DN mechanistic studies. A diabetes model was established by feeding miniature pigs with high-sugar and high-fat diets. Functional and pathological markers, expression and activation of endogenous TLR ligands [HSP70 (heat shock protein 70) and HMGB1], TLR1 to TLR11 and their downstream signaling pathway molecules (MyD88, IRAK-1, and IRF-3), nuclear factor ?B (NF-?B) signaling pathway molecules (IKK?, I?B?, and NF-?Bp65), inflammatory cytokines [IL-6 (interleukin-6), MIP-2, MCP-1, CCL5, and VCAM-1 (vascular cell adhesion molecule-1)], and infiltration of inflammatory cells were systematically evaluated. The expression of HSP70 was significantly increased in diabetic pig kidneys. The expression of MyD88-dependent TLR2, TLR4, TLR5, TLR7, TLR8, and TLR11 and their downstream signaling molecules MyD88 and phospho-IRAK-1 (activated IRAK-1), as well as that of MyD88-independent TLR3 and TLR4 and their downstream signaling molecule phospho-IRF-3 (activated IRF-3), was significantly up-regulated. The expression and activation of NF-?B pathway molecules phospho-IKK?, phospho-I?B?, NF-?Bp65, and phospho-NF-?Bp65 were significantly increased. Levels of IL-6, MIP-2, MCP-1, CCL5, VCAM-1, and macrophage marker CD68 were significantly increased in diabetic pig kidneys. These results suggested that the metabolic inflammation activated by TLRs might play an important role in diabetic renal injuries.

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Developmental expression of Toll?like receptors in the guinea pig lung.

Publications

Developmental expression of Toll‑like receptors in the guinea pig lung.

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