Pharmacologic augmentation of hypoxia-inducible factor-1alpha with mimosine boosts the bactericidal capacity of phagocytes.

نویسندگان

  • Annelies S Zinkernagel
  • Carole Peyssonnaux
  • Randall S Johnson
  • Victor Nizet
چکیده

Hypoxia-inducible factor (HIF)-1alpha is activated on exposure to bacterial pathogens and regulates the innate immune functions of phagocytes. We show here that the HIF-1alpha agonist mimosine can boost the capacity of human phagocytes and whole blood to kill the leading pathogen Staphylococcus aureus in a dose-dependent fashion and reduce the lesion size in a murine model of S. aureus skin infection. This provides the first proof of principle for a novel approach to the treatment of bacterial infection by pharmacologically augmenting the host phagocytic function.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Pharmacologic Augmentation of Hypoxia-Inducible Factor–1 with Mimosine Boosts the Bactericidal Capacity of Phagocytes

Hypoxia-inducible factor (HIF)–1 is activated on exposure to bacterial pathogens and regulates the innate immune functions of phagocytes. We show here that the HIF-1 agonist mimosine can boost the capacity of human phagocytes and whole blood to kill the leading pathogen Staphylococcus aureus in a dose-dependent fashion and reduce the lesion size in a murine model of S. aureus skin infection. Th...

متن کامل

HIF-1α expression regulates the bactericidal capacity of phagocytes

Hypoxia is a characteristic feature of the tissue microenvironment during bacterial infection. Here we report on our use of conditional gene targeting to examine the contribution of hypoxia-inducible factor 1, α subunit (HIF-1α) to myeloid cell innate immune function. HIF-1α was induced by bacterial infection, even under normoxia, and regulated the production of key immune effector molecules, i...

متن کامل

Critical role of HIF-1alpha in keratinocyte defense against bacterial infection.

Skin, the first barrier against invading microorganisms, is hypoxic, even under baseline conditions. The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha, the principal regulator of cellular adaptation to low oxygen, is strongly expressed in skin epithelium. HIF-1alpha is now understood to play a key role in the bactericidal capacity of phagocytic cells such as macrophages and n...

متن کامل

Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys.

Hypoxia inducible factor (HIF) prolyl-4-hydroxylase domain-containing proteins (PHDs) promote the degradation of HIF-1alpha. Because HIF-1alpha is highly expressed in the renal medulla and HIF-1alpha-targeted genes such as nitric oxide synthase, cyclooxygenase, and heme oxygenase are important in the regulation of renal medullary function, we hypothesized that PHD regulates HIF-1alpha levels in...

متن کامل

تأثیر یک دوره تمرین استقامتی شنا بر سطوح القایی‌هایپوکسی کبد موش‌های باردار در معرض مسمومیت کادمیوم

  Background and Objective: The physiological changes in liver function in pregnancy are commonly transient and are rarely permanent. HIFs are important to treatment of injuries,inflammation and response to hypoxia. However exercise in pregnancy and some of environmental toxicities can influence HIF levels.The goal of this study was identification of endurance swimming by identifying HIF-1 prot...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of infectious diseases

دوره 197 2  شماره 

صفحات  -

تاریخ انتشار 2008