Induced expression of Toll-like receptor 9 in peritubular capillary endothelium correlates with the progression of tubulointerstitial lesions in autoimmune disease-prone mice.

BACKGROUND: Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood-urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of peritubular capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice. METHODS: Lupus-prone BXSB/MpJ-Yaa (Yaa) and BXSB/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis. RESULTS: Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24 wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24 wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta ( Il1b), Il6, interferon gamma ( Ifng), and tumor necrosis factor alpha ( Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24 wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24 wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules ( P < 0.05 and 0.01). CONCLUSION: Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.

Genetic factors derived from the MRL/MpJ mouse function to maintain the integrity of spermatogenesis after heat exposure.

MRL/MpJ mice possess highly heat-shock-resistant spermatocytes (HRS) in comparison with C57BL/6 mice. This resistance depends on the MRL/MpJ-type loci at the 81 cM region of Chromosome (Chr) 1 and the 40 cM region of Chr 11. To evaluate the functions of these loci in detail, we examined the histopathological changes resulting from experimental cryptorchidism or transient scrotal heat stress (SHS) in the testes of C57BL/6-based congenic strains (B6.MRLc1, B6.MRLc11, and B6.MRLc1c11) carrying the MRL/MpJ-derived loci responsible for HRS. Among cryptorchid testes from congenic strains, those in B6.MRLc1c11 mice showed the highest heat resistance, indicating that the genetic interactions between MRL/MpJ-derived HRS loci on Chrs 1 and 11 may be important for maintaining spermatogenesis under continuous testicular hyperthermia. In contrast, immediately after SHS induction, germ cell loss via apoptosis was inhibited in B6.MRLc11 and B6.MRLc1c11 mice, similar to that in MRL/MpJ mice. However, this HRS phenotype was not observed in C57BL/6 or B6.MRLc1 mice after SHS induction. Furthermore, testicular calcification owing to long-term damage by SHS induction was inhibited in all congenic strains in comparison with that in C57BL/6 mice, indicating that each MRL/MpJ-derived locus on Chrs 1 and 11 acted independently to facilitate the recovery of heat-induced testicular damage by inhibiting calcification. B6.MRLc11 and B6.MRLc1c11 mice showed greater recovery in spermatogenesis than B6.MRLc1 mice 60 days after SHS induction. Therefore, the MRL/MpJ-derived HRS locus on Chr 11 might play an important role in recovery from heat stress damage. On the basis of these results, we concluded that MRL/MpJ-derived loci on Chrs 1 and 11 cooperatively or independently regulate testicular heat sensitivity depending on the various heat stresses.

Structural changes of goat parotid salivary gland: pre- and post-weaning periods.

Previously, the structure of the adult goat parotid salivary glands (PGs) was studied. However, little information was elucidated of the juvenile ones. This study aimed to clarify the correlations between the structure of goats' PGs and the nature of food intake among milk-suckling kids (MSKs) and diet-fed goats (DFGs). The secretory endpieces of the goats' PGs are of the pure serous type. The serous cells in MSKs showed apical accumulation of numerous secretory granules (SGs) of smaller size and of more intense positive periodic acid-Schiff reaction. Ultrastructurally, most of the SGs in the DFGs contained peripherally located inclusions that showed dense reaction products for acid phosphatase. In MSKs, the PGs showed less-developed basal infoldings, sparseness of the inter-cellular inter-digitations, fewer inter-cellular canaliculi and microvilli and also less-developed myoepithelial cells with fewer and shorter cytoplasmic processes. In conclusion, the less-developed membrane specializations and myoepithelial cells, as well as the accumulated SGs in the PGs of MSKs, suggest that it secretes less saliva with a little secretory activity than that of DFGs, which may be correlated with the reduced masticatory activity.