Related Experiment Video
Updated: Jun 19, 2026
09:25
Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
The IL-8 production by Streptococcal pyrogenic exotoxin B
Chia-Wen Chang1, Siang-Yu Wu, Woei-Jer Chuang
1Institute of Basic Medical Sciences, Department of Biochemistry, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
Experimental Biology and Medicine (Maywood, N.J.)
|October 27, 2009
Summary
Streptococcal pyrogenic exotoxin B (SPE B) induces IL-8 production via the Fas receptor pathway. This involves activating FADD, caspase 8, ERK, and NF-kappaB signaling in A549 cells.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Streptococcal pyrogenic exotoxin B (SPE B) is known to interact with alpha(v)beta(3) and Fas receptors.
- A specific mutant, G308S, interacts exclusively with the Fas receptor.
- The mechanism by which SPE B induces Interleukin-8 (IL-8) production remains to be fully elucidated.
Purpose of the Study:
- To investigate the cellular interactions and signaling pathways by which SPE B induces IL-8 production.
- To determine the role of the Fas receptor in SPE B-mediated IL-8 induction.
- To elucidate the downstream signaling cascade involving FADD, caspase 8, ERK, and NF-kappaB.
Main Methods:
- Exposure of A549 cells to SPE B and its mutant G308S.
- Measurement of IL-8 protein and mRNA levels.
- Use of anti-Fas antibody and siRNA targeting FADD and procaspase 8.
- Assessment of FADD-procaspase 8 association, NF-kappaB activation, and ERK phosphorylation.
- Analysis of MEKK1 cleavage and its interaction with caspase 8.
Main Results:
- Both SPE B and G308S significantly increased IL-8 protein and mRNA levels, an effect inhibited by anti-Fas antibody.
- G308S induced FADD-procaspase 8 association and NF-kappaB activation, which were dependent on FADD and procaspase 8.
- Caspase 8 proteolytic activity was essential for NF-kappaB activation.
- G308S promoted ERK phosphorylation and NF-kappaB nuclear translocation; ERK inhibition reduced IL-8 production and NF-kappaB activity.
- Procaspase 8 siRNA blocked G308S-induced MEKK1 cleavage, MEKK1-caspase 8 binding, ERK activation, and NF-kappaB activity.
Conclusions:
- SPE B-induced IL-8 production in A549 cells is primarily mediated through the Fas receptor.
- The signaling pathway involves the sequential activation of FADD, caspase 8, MEKK1, ERK, and NF-kappaB.
- This study clarifies the molecular mechanism of SPE B's inflammatory response induction.
Related Concept Videos
01:27Streptococcal Pharyngitis
Streptococcal pharyngitis, commonly known as “strep throat,” is an acute infection of the oropharyngeal tissues caused by the Gram‑positive Group A Streptococcus (Streptococcus pyogenes). Transmission occurs primarily through respiratory droplets expelled during coughing, sneezing, or talking.Mechanisms of Host Entry and Immune EvasionUpon entering the host, S. pyogenes adheres to the mucosal epithelial cells of the pharynx via surface proteins, notably lipoteichoic acid and the antiphagocytic...
01:20Determinants of Bacterial Pathogenicity and Virulence
Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...
01:28Diphtheria
Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific β-corynephage. This phage...
01:12Bacterial Toxins
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
01:25Inhalation Anthrax
Anthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive, spore-forming bacterium. It primarily affects herbivorous animals but can be transmitted to humans through skin contact, ingestion, or inhalation of spores.Cutaneous anthrax, the most common form, typically results from direct contact with bacterial spores through skin abrasions and is generally less severe. Gastrointestinal anthrax results from eating undercooked or contaminated meat. It affects the mouth, throat, or...
01:26Bacterial Meningitis II: Pathophysiology
Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...