Yafang Huang - Academia.edu (original) (raw)
Related Authors
Universidade Estadual Paulista "Júlio de Mesquita Filho"
Uploads
Papers by Yafang Huang
Antioxidants & Redox Signaling, 2015
Aims: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets... more Aims: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress. Results: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1-/mice, a mouse strain lacking the expression of the NCF1/p47 phox component of NOX2. The levels of interleukin-1b (IL-1b) and IL-6 in inflamed joints were higher in Ncf1-/than in controls. Antagonists of tumor necrosis factor-a (TNFa) and IL-1b were equally effective in suppressing arthritis in wild-type mice, while IL-1b blockade was more effective than TNFa blockade in Ncf1-/mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1-/mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1b to its active form and this activity was suppressed by ROS. Innovation: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS. Conclusion: Our results suggest that ROS act as a negative feedback to constrain IL-1b-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2. Antioxid. Redox Signal. 23, 973-984.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2002
Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by defects in... more Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by defects in leukocyte NADPH oxidase. Various inherited defects in one of the membrane-bound components of NADPH oxidase, gp91-phox, cause Xlinked (X91) CGD. Analysis of three patients with X91 CGD revealed that different mechanisms of molecular quality control lead to the common phenotype of absence of mature membrane-bound NADPH oxidase complex in leukocytes. In the first patient, aberrant intron splicing created a premature stop codon. However, the mutant mRNA was degraded prematurely, which prevented the production of truncated protein. In the second patient, a frameshift mutation with the potential to generate a gp91-phox polypeptide, with an aberrant and elongated C-terminus, led to barely detectable levels of gp91-phox, even though the reported functional domains of the protein appeared unaffected. In the third patient, a point mutation created a single amino acid change in the predicted FAD-binding site of gp91-phox. Although gp91-phox was detectable with Western blotting, no cytochrome b 558 was expressed on the cell surface. These analyses showed that molecular quality control machinery plays an important role in the pathogenesis of CGD, not only in the X91 0 but also in the X91 3 form of this Xlinked disease.
Antioxidants & Redox Signaling, 2015
Aims: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets... more Aims: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress. Results: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1-/mice, a mouse strain lacking the expression of the NCF1/p47 phox component of NOX2. The levels of interleukin-1b (IL-1b) and IL-6 in inflamed joints were higher in Ncf1-/than in controls. Antagonists of tumor necrosis factor-a (TNFa) and IL-1b were equally effective in suppressing arthritis in wild-type mice, while IL-1b blockade was more effective than TNFa blockade in Ncf1-/mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1-/mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1b to its active form and this activity was suppressed by ROS. Innovation: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS. Conclusion: Our results suggest that ROS act as a negative feedback to constrain IL-1b-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2. Antioxid. Redox Signal. 23, 973-984.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2002
Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by defects in... more Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by defects in leukocyte NADPH oxidase. Various inherited defects in one of the membrane-bound components of NADPH oxidase, gp91-phox, cause Xlinked (X91) CGD. Analysis of three patients with X91 CGD revealed that different mechanisms of molecular quality control lead to the common phenotype of absence of mature membrane-bound NADPH oxidase complex in leukocytes. In the first patient, aberrant intron splicing created a premature stop codon. However, the mutant mRNA was degraded prematurely, which prevented the production of truncated protein. In the second patient, a frameshift mutation with the potential to generate a gp91-phox polypeptide, with an aberrant and elongated C-terminus, led to barely detectable levels of gp91-phox, even though the reported functional domains of the protein appeared unaffected. In the third patient, a point mutation created a single amino acid change in the predicted FAD-binding site of gp91-phox. Although gp91-phox was detectable with Western blotting, no cytochrome b 558 was expressed on the cell surface. These analyses showed that molecular quality control machinery plays an important role in the pathogenesis of CGD, not only in the X91 0 but also in the X91 3 form of this Xlinked disease.