Related Experiment Video

Updated: Feb 15, 2026

The Benthic Exchange of O2, N2 and Dissolved Nutrients Using Small Core Incubations
10:11

The Benthic Exchange of O2, N2 and Dissolved Nutrients Using Small Core Incubations

Published on: August 3, 2016

10.4K

Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory Cytokines Expression Through the

Yawen Niu1, Guiqiu Zhao1, Cui Li1

  • 1Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.

Investigative Ophthalmology & Visual Science
|January 15, 2018
PubMed
Abstract

Insights

Aspergillus fumigatus infection increases protease-activated receptor-2 (PAR-2) in the cornea, leading to inflammation and disease. Blocking PAR-2 with FSLLRY-NH2 reduces these effects, suggesting PAR-2 is a key target for treating fungal keratitis.

Area of Science:

  • Ophthalmology
  • Infectious Diseases
  • Immunology

Background:

  • Fungal keratitis, particularly Aspergillus fumigatus infections, poses a significant threat to vision.
  • The role of specific inflammatory pathways, such as protease-activated receptor-2 (PAR-2), in fungal keratitis pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of protease-activated receptor-2 (PAR-2) in the ocular immune response to Aspergillus fumigatus infection in a mouse model.
  • To evaluate the therapeutic potential of a PAR-2 antagonist in mitigating fungal keratitis.

Main Methods:

  • Mice corneas were infected with A. fumigatus, with or without pretreatment with the PAR-2 antagonist FSLLRY-NH2.
  • Disease severity, polymorphonuclear neutrophilic leukocyte (PMN) infiltration, and expression of inflammatory mediators (IL-1β, TNF-α, IFN-γ, MIP-2) and p-ERK1/2 were assessed.
  • PAR-2 expression was analyzed in corneal tissue and stimulated PMNs.

Main Results:

  • A. fumigatus infection significantly upregulated PAR-2 expression in mouse corneas and PMNs.
  • Treatment with the PAR-2 antagonist FSLLRY-NH2 significantly reduced disease severity, PMN infiltration, and the expression of key proinflammatory cytokines.
  • FSLLRY-NH2's inhibitory effects on cytokine production may involve the p-ERK1/2 signaling pathway.

Conclusions:

  • Protease-activated receptor-2 (PAR-2) plays a crucial role in mediating the inflammatory response and disease progression during Aspergillus fumigatus keratitis.
  • Inhibition of PAR-2 with FSLLRY-NH2 demonstrates a promising therapeutic strategy for reducing inflammation and tissue damage in fungal eye infections.
  • The findings suggest that targeting PAR-2, potentially through modulation of the p-ERK1/2 pathway, could be beneficial in managing fungal keratitis.

More Related Videos

Measuring Phagocytosis of Aspergillus fumigatus Conidia by Human Leukocytes using Flow Cytometry09:43

Measuring Phagocytosis of Aspergillus fumigatus Conidia by Human Leukocytes using Flow Cytometry

Published on: December 7, 2019

7.4K
PAR-CliP - A Method to Identify Transcriptome-wide the Binding Sites of RNA Binding Proteins12:24

PAR-CliP - A Method to Identify Transcriptome-wide the Binding Sites of RNA Binding Proteins

Published on: July 2, 2010

54.2K

Related Concept Videos

meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H01:13

meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H

All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for...
6.8K
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
5.5K
SN2 Reaction: Kinetics02:14

SN2 Reaction: Kinetics

Kinetic Studies and Significance
In a chemical reaction, a relationship exists between the concentration of reactants and the rate at which the reaction proceeds. The study to measure this relationship is known as the kinetics of a chemical reaction. Kinetic studies are used to deduce the rate law of a chemical reaction, which provides information about the species involved during the transition state of the rate-determining step. Thus, kinetic studies help to derive the mechanism of a...
10.4K
SN2 Reaction: Mechanism02:27

SN2 Reaction: Mechanism

The kinetic studies of SN2 reactions suggest an essential feature of its mechanism: it is a single-step process without intermediates. Here, both the nucleophile and the substrate participate in the rate-determining step.
The presence of the more electronegative halogen in the substrate creates a polarized carbon-halide bond. The halide pulls the electron cloud generating an electrophilic center at the carbon atom. Thus, the carbon atom carries a partial positive charge while the halide has a...
17.6K
SN2 Reaction: Transition State02:26

SN2 Reaction: Transition State

An SN2 reaction of an alkyl halide is a single-step process in which bond formation between the nucleophile and the substrate and bond breaking between the substrate and the halide occurs simultaneously through a transition state without forming an intermediate.
When the nucleophile approaches the electrophilic carbon with its lone pairs, the halide acts as a leaving group and moves away with the electron-pair bonded to the carbon. Dotted partial bonds represent the bonds being formed or broken...
12.1K
SN2 Reaction: Stereochemistry02:23

SN2 Reaction: Stereochemistry

In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not...
11.9K