Lupus Disease In Mice Research Articles

In Vivo Remodeling of Altered Autophagy-Lysosomal Pathway by a Phosphopeptide in Lupus.

The phosphopeptide P140/Lupuzor, which improves the course of lupus disease in mice and patients, targets chaperone-mediated autophagy (CMA), a selective form of autophagy that is abnormally upregulated in lupus-prone MRL/lpr mice. Administered intravenously to diseased mice, P140 reduces the expression level of two major protein players of CMA, LAMP2A and HSPA8, and inhibits CMA in vitro in a cell line that stably expresses a CMA reporter. Here, we aimed to demonstrate that P140 also affects CMA in vivo and to unravel the precise cellular mechanism of how P140 interacts with the CMA process. MRL/lpr mice and CBA/J mice used as control received P140 or control peptides intravenously. Lysosome-enriched fractions of spleen or liver were prepared to examine lysosomal function. Highly purified lysosomes were further isolated and left to incubate with the CMA substrate to study at which cellular step P140 interacts with the CMA process. The data show that P140 effectively regulates CMA in vivo in MRL/lpr mice at the step of substrate lysosomal uptake and restores some alterations of defective lysosomes. For the first time, it is demonstrated that by occluding the intralysosome uptake of CMA substrates, a therapeutic molecule can attenuate excessive CMA activity in a pathological pro-inflammatory context and protect against hyperinflammation. This recovery effect of P140 on hyperactivated CMA is not only important for lupus therapy but potentially also for treating other (auto)inflammatory diseases, including neurologic and metabolic disorders, where CMA modulation would be highly beneficial.

Evaluation of Ethanolic Extracts of Mullaca (Physalis Angulata L.) Herbs for Treatment of Lupus Disease in Mice Induced Pristane

Systemic lupus erythematosus is a systemic autoimmune disease characterized by multisystem inflammation due to immune complex deposits in the organs like kidneys, joints, pleura, skin, and so on. Physalisangulata known as mullaca, has been widely studied for its pharmacological activities such as antiinflammatory, immunosuppressive, cytotoxic, and also inhibition of organ rejection in transplantation. This study was directed to investigate the activities of P. angulata extract as an immunomodulatory agent. P. angulata powder was extracted by maceration with 70% of ethanol. An animal model of lupus was obtained by an injection 0.7mL of pristane, i.p. Successful induction obtained in two weeks after injection which can be monitored by measuring total leukocyte count. For ensuring successful induction, another test was done four weeks and eight weeks after injection by detecting the presence of specific antinuclear antibodies using SDS PAGE method. Other measured parameters were including nonspecific immune response (measurement of total leukocyte count and differential leukocyte count), specific humoral immune response (hemagglutination test), specific cellular immune responses (delayed type hypersensitivity test), organ index and histology of kidney and spleen. As the results shown, ethanolic extract of Physalisangulata at dose of 1000mg/kg BW orally, gave immunomodulatory effect in Lupus rat model. The extract worked primarily on specific immune response by lowering immune response near to the normal value, it was not suppressing immune response as prednisone.