ABSTRACT
Objective@#Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by the production of autoantibodies and high cholesterol levels. HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors have exhibited anti-inflammatory effects in several clinical trials. We conducted this study to evaluate the effect of rosuvastatin on inflammatory responses in lupus-prone mice. @*Methods@#MRL/lpr mice were intraperitoneally injected with rosuvastatin (10 mg/kg, n=4) or vehicle (2% dimethyl sulfoxide, n=4) five times a week from 13 to 17 weeks of age. The serum levels of low-density lipoprotein (LDL) cholesterol and autoantibodies were measured, as well as the urine levels of albumin. Renal tissues were stained for histopathological analysis. Concentrations of key inflammatory cytokines were measured in the serum, and messenger RNA (mRNA) levels in target organs (kidney, spleen, and lymph nodes) were evaluated. @*Results@#Rosuvastatin treatment significantly decreased serum LDL cholesterol concentration in MRL/lpr mice. However, the clinical manifestations and autoantibody titres did not improve with rosuvastatin treatment. In addition, serum inflammatory cytokines and proteinuria did not change. Histopathological analysis of the kidneys revealed no improvement. When assessing the expression of mRNA, treatment with rosuvastatin decreased tumor necrosis alpha and interleukin-17 concentration in spleen and kidney tissue and in the kidneys and lymph nodes of MRL/lpr mice, respectively. @*Conclusion@#Although it can decrease inflammatory cytokines in the lymphoid organs and kidneys of MRL/lpr mice, treatment with rosuvastatin is insufficient to alleviate SLE.
ABSTRACT
Objective@#Systemic lupus erythematosus (SLE) is a common chronic autoimmune inflammatory disease. According to recent studies, signaling through Toll-like receptor (TLR) protein, which promotes the production of inflammatory cytokines, leads to the development of SLE. TLR-inhibitory peptide 1 (TIP1) has been newly identified for the treatment of autoimmune diseases. @*Methods@#The effect of TIP1 was analyzed in an SLE mouse model (MRL/lpr). The mice in the control treatment group (n=5) were administered an intravenous injection of phosphate-buffered saline twice weekly, whereas the mice in the TIP1 treatment group (n=6) were administered an intravenous injection of TIP1 (1 nmol/g) twice weekly. MRL/mpj mice (n=5) were selected as normal controls. The mice were injected for 4 weeks between 14 and 18 weeks of age, followed by assays of their spleen, kidneys, lymph nodes, serum, and urine. @*Results@#The antinuclear antibody and inflammatory cytokine (interferon-α) in the serum as well as levels of albumin in the urine of the mice in the TIP1 treatment group had decreased when compared to those of mice in the control treatment group. Kidney inflammation in mice in the TIP1 treatment group was alleviated. The mRNA expression levels of TLR7- or TLR9-related downstream signaling molecules also decreased in all organs of the mice in the TIP1treatment group. @*Conclusion@#Intravenous treatment with TIP1 reduces symptoms and markers of inflammation in MRL/lpr mice. Hence, TIP1 is a promising medication for the treatment of SLE.
ABSTRACT
Objective@#Systemic lupus erythematosus (SLE) is a common chronic autoimmune inflammatory disease. According to recent studies, signaling through Toll-like receptor (TLR) protein, which promotes the production of inflammatory cytokines, leads to the development of SLE. TLR-inhibitory peptide 1 (TIP1) has been newly identified for the treatment of autoimmune diseases. @*Methods@#The effect of TIP1 was analyzed in an SLE mouse model (MRL/lpr). The mice in the control treatment group (n=5) were administered an intravenous injection of phosphate-buffered saline twice weekly, whereas the mice in the TIP1 treatment group (n=6) were administered an intravenous injection of TIP1 (1 nmol/g) twice weekly. MRL/mpj mice (n=5) were selected as normal controls. The mice were injected for 4 weeks between 14 and 18 weeks of age, followed by assays of their spleen, kidneys, lymph nodes, serum, and urine. @*Results@#The antinuclear antibody and inflammatory cytokine (interferon-α) in the serum as well as levels of albumin in the urine of the mice in the TIP1 treatment group had decreased when compared to those of mice in the control treatment group. Kidney inflammation in mice in the TIP1 treatment group was alleviated. The mRNA expression levels of TLR7- or TLR9-related downstream signaling molecules also decreased in all organs of the mice in the TIP1treatment group. @*Conclusion@#Intravenous treatment with TIP1 reduces symptoms and markers of inflammation in MRL/lpr mice. Hence, TIP1 is a promising medication for the treatment of SLE.
ABSTRACT
OBJECTIVES: Osterix (Osx) is an important transcription factor for bone formation which was identified through the study of Osx homozygous null mutants showing a complete absence of intramembranous and endochondral bone formation. However, due to the immediate death of Osx null mutants in the perinatal period, it is not possible to determine the role of Osx after birth. To study whether Osx is essential for bone formation and maintenance after birth, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP recombination system. In a previous study, Osx inactivation with 2.3-kb Col1a1-Cre exhibited the osteopenic phenotype in growing bones with an increase in early marker genes for osteoblast differentiation and a reduction of the late marker gene. Here, the difference of Osx downstream target genes was examined in Osx-inactivated mice with Col1a1-Cre. MATERIALS & METHODS: To further elucidate the difference in Osx downstream target genes in skeletal development, Osx-inactivated mice with 2.3-kb Col1a1-Cre were generated by crossing with conditional Osx knockout mice and 2.3-kb Col1a1-Cre. DNA microarray analysis was conducted in the long bones of these mice. RESULTS: Osx-inactivated mice were generated with a disorganization of collagen layer in bone phenotype, which was shown in a previous report. In Osx-inactivated bones, genes required for bone formation, such as Dlx, Smad, and Runx2, were increased, whereas cartilage-related genes were decreased. CONCLUSIONS: These results indicate that gene alterations by Osx expression will provide an understanding of the change in the in vivo microenvironment during postnatal bone formation and maintenance.