ABSTRACT
INTRODUCTION: Renal damage is a consequence of severe malaria, and is generally caused by sequestration of Plasmodium falciparum -infected erythrocytes in the renal microcirculation, which leads to obstruction, hypoxia, and ischemia. This triggers high mobility group box 1 (HMGB1) to send a danger signal through toll-like receptors 2 and 4. This signal up-regulates inducible nitric oxide (iNOS) and nitrotyrosine to re-perfuse the tissue, and also increases heat shock protein 70 (HSP70) expression. As no study has examined the involvement of intracellular secondary molecules in this setting, the present study compared the renal expressions of HSP70, HMGB1, iNOS, and nitrotyrosine between mice suffered from severe malaria and normal mice. METHODS: C57BL/6 mice were divided into an infected group (intraperitoneal injection of 10 6 P. berghei ANKA) and a non-infected group. Renal damage was evaluated using hematoxylin eosin staining, and immunohistochemistry was used to evaluate the expressions of HSP70, HMGB1, iNOS, and nitrotyrosine. RESULTS: Significant inter-group differences were observed in the renal expressions of HSP70, HMGB1, and iNOS (p=0.000, Mann-Whitney test), as well as nitrotyrosine (p=0.000, independent t test). The expressions of HSP70 and HMGB1 were strongly correlated (p=0.000, R=1.000). No correlations were observed between iNOS and HMGB, HMGB1 and nitrotyrosine, HSP70 and nitrotyrosine, or iNOS and nitrotyrosine. CONCLUSIONS: It appears that HMGB1, HSP70, iNOS, and nitrotyrosine play roles in the renal damage that is observed in mice with severe malaria. Only HSP70 expression is strongly correlated with the expression of HMGB1.
Subject(s)
Acute Kidney Injury/parasitology , HMGB1 Protein/metabolism , HSP70 Heat-Shock Proteins/metabolism , Malaria/complications , Malaria/metabolism , Nitric Oxide Synthase Type II/metabolism , Tyrosine/analogs & derivatives , Animals , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , Severity of Illness Index , Tyrosine/metabolismABSTRACT
Abstract INTRODUCTION Renal damage is a consequence of severe malaria, and is generally caused by sequestration of Plasmodium falciparum -infected erythrocytes in the renal microcirculation, which leads to obstruction, hypoxia, and ischemia. This triggers high mobility group box 1 (HMGB1) to send a danger signal through toll-like receptors 2 and 4. This signal up-regulates inducible nitric oxide (iNOS) and nitrotyrosine to re-perfuse the tissue, and also increases heat shock protein 70 (HSP70) expression. As no study has examined the involvement of intracellular secondary molecules in this setting, the present study compared the renal expressions of HSP70, HMGB1, iNOS, and nitrotyrosine between mice suffered from severe malaria and normal mice. METHODS C57BL/6 mice were divided into an infected group (intraperitoneal injection of 10 6 P. berghei ANKA) and a non-infected group. Renal damage was evaluated using hematoxylin eosin staining, and immunohistochemistry was used to evaluate the expressions of HSP70, HMGB1, iNOS, and nitrotyrosine. RESULTS Significant inter-group differences were observed in the renal expressions of HSP70, HMGB1, and iNOS (p=0.000, Mann-Whitney test), as well as nitrotyrosine (p=0.000, independent t test). The expressions of HSP70 and HMGB1 were strongly correlated (p=0.000, R=1.000). No correlations were observed between iNOS and HMGB, HMGB1 and nitrotyrosine, HSP70 and nitrotyrosine, or iNOS and nitrotyrosine. CONCLUSIONS It appears that HMGB1, HSP70, iNOS, and nitrotyrosine play roles in the renal damage that is observed in mice with severe malaria. Only HSP70 expression is strongly correlated with the expression of HMGB1.
Subject(s)
Animals , Female , Tyrosine/antagonists & inhibitors , HSP70 Heat-Shock Proteins/metabolism , HMGB1 Protein/metabolism , Nitric Oxide Synthase Type II/metabolism , Acute Kidney Injury/parasitology , Malaria/complications , Malaria/metabolism , Tyrosine/metabolism , Severity of Illness Index , Disease Models, Animal , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: We aimed to reveal the role of CD11b and hypoxia-inducible factors-1alpha (HIF-1α) expressions on monocytes and alveolar macrophages of lung tissue, and the levels of serum surfactant protein-D (SP-D) in severe malaria-associated acute lung injury (ALI). METHODS: The C57BL/6 mice were divided into control group, renal malaria group (inoculated with 106Plasmodium berghei ANKA), and cerebral malaria group (inoculated with 107P. berghei ANKA). The expressions of CD11b and HIF-1α in lung tissue were observed by immunohistochemistry, and serum SP-D levels were measured by ELISA. This study was conducted from June 2014 to February 2015 in the Laboratory of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang. RESULTS: The CD11b expression on pulmonary tissue of renal and cerebral malaria mice were significantly higher than control mice (P=0.002; P=0.002), as well as the HIF-1α expression on pulmonary tissue (P=0.002; P=0.002). The level of serum SP-D in renal malaria and cerebral malaria mice were significantly higher than control mice (P=0.002; P=0.002). We found a strong correlation between the expression of CD11b and HIF-1α in lung tissue (r=0.937, P=0.000), as well as between CD11b expression and serum SP-D levels (r=0.907, P=0.000) and between HIF-1α expression and serum SP-D levels (r=0.913, P=0.000). CONCLUSION: Severe malaria-associated ALI increased the expression of CD11b and HIF-1α in the lung tissue and increased serum SP-D levels of C57BL/6 mice significantly.
