The Agonists of Formyl Peptide Receptors Prevent Development of Severe Sepsis after Microbial Infection

Kim, Sang Doo; Kim, Eui Chong; Lee, Ha Young; Kim, You-Sun; Jeon, Seong Gyu; Baek, Suk‐Hwan; Song, Dong‐Keun; Ryu, Sung Ho; Bae, Yoe‐Sik

doi:10.4049/jimmunol.1001310

Cited by 59 publications

(62 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies suggest that W-peptide treatment reduces systemic levels of proinflammatory cytokines, such as TNF-a and IL-1b, in a sepsis mice model (11). The present study showed that FPRs (fpr1 and fpr2) were expressed in mouse lung tissues (Fig.…”

Section: Effects Of Fpr Activation On Mediator Release From Macrophagessupporting

confidence: 60%

“…Moreover, activation of FPRs using its synthetic agonist modulated systemic inflammation and immune responses in a sepsis model (11). In the current study, we demonstrated that airway activation of FPRs during sensitization significantly inhibited lung inflammation accompanied by downregulation of mediator release, which could exacerbate inflammation.…”

Section: Discussionsupporting

confidence: 48%

“…It was recently reported that the expression of FPRs is essential for early host defense to bacterial infections (10). Moreover, we demonstrated that FPR activation prevented the progression of sepsis in a sepsis animal model (11).…”

mentioning

confidence: 50%

“…An in vitro assay demonstrated that W-peptide induced the chemotactic migration of phagocytes, enhanced the bactericidal activity of monocytes and neutrophils via the production of superoxide anions, and blocked cell apoptosis (19)(20)(21)(22). Furthermore, W-peptide effectively prevented development of severe sepsis following microbial infection via modulation of inflammation and immune responses (11).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Airway Activation of Formyl Peptide Receptors Inhibits Th1 and Th17 Cell Responses via Inhibition of Mediator Release from Immune and Inflammatory Cells and Maturation of Dendritic Cells

Tae

Park

Moon

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Formyl peptide receptors (FPRs) are chemoattractant receptors that mediate inflammatory cell responses to infection. Recent evidence indicates that noneosinophilic asthma phenotypes can be developed by both Th1 and Th17 cell responses when exposed to LPS-containing allergens. In this study, we evaluated the effects of airway activation of FPRs by their synthetic agonist, Trp-Lys-Tyr-Met-Val-D-Met (W-peptide), on the development of Th1 and Th17 cell responses in a noneosinophilic asthma mouse model. A noneosinophilic asthma mouse model was generated by intranasal sensitization with 10 μg of LPS plus 75 μg of OVA on days 0, 1, 2, and 7. Mice were then challenged with 50 μg of OVA alone on days 14, 15, 21, and 22. W-peptide was administered during the sensitization period, and immune and inflammatory responses were evaluated after OVA challenge. Lung inflammation after OVA challenge was partly abolished by airway activation of FPRs during sensitization. Maturation of dendritic cells (DCs) and migration of DCs from the lung to lung-draining lymph nodes were inhibited by FPR activation. In addition, airway activation of FPRs inhibited allergen-specific T cell proliferation in the lymph nodes. Production of IL-12 and IL-6 (Th1- and Th17-polarizing cytokines) from lung DCs was decreased by airway activation of FPRs. This effect resulted in the inhibition of allergen-specific Th1 and Th17 cell responses. Airway activation of FPRs during sensitization effectively prevents the development of Th1 and Th17 cell responses induced by LPS-containing allergens via multiple mechanisms, such as inhibition of DC maturation and migration and the production of Th1- and Th7-polarizing cytokines.

show abstract

Section: Effects Of Fpr Activation On Mediator Release From Macrophagessupporting

confidence: 60%

Section: Discussionsupporting

confidence: 48%

mentioning

confidence: 50%

mentioning

confidence: 99%

See 2 more Smart Citations

Airway Activation of Formyl Peptide Receptors Inhibits Th1 and Th17 Cell Responses via Inhibition of Mediator Release from Immune and Inflammatory Cells and Maturation of Dendritic Cells

Tae

Park

Moon

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Control of the immune response by CR-Ac 2-50 was complemented by a significant attenuation of the impairment in systolic contractility. This effect can reflect an indirect protection through reduced inflammation but also could be the consequence of a direct protective action on the myocardium, preserving its contractile function (45,46). None of these biological properties were retained in Fpr2/3 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

Gobbetti

Coldewey

Chen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

104

103

View full text Add to dashboard Cite

Significance Sepsis defines a syndrome with poor clinical management characterized by overlapping phases of excessive inflammation temporally aligned with an immunosuppressed state. We define an endogenous pathway centered on formyl-peptide receptor 2/3 (Fpr2/3)—ortholog to human FPR2/ALX (receptor for lipoxin A4)—that protects the host against polymicrobial sepsis. Using null mice and proof-of-concept experiments with a peptide–agonist, we demonstrate how engagement of Fpr2/3 is crucial to enact nonredundant functions that span from control of cell recruitment and phagocytosis, modulation of soluble mediator generation, to containment of bacteremia, thus preventing spreading to vital organs and opening new opportunities to manipulate the host response in sepsis.

show abstract

Drug Repositioning to Alleviate Systemic Inflammatory Response Syndrome Caused by Gram‐Negative Bacterial Outer Membrane Vesicles

Kim

Lee

Park

et al. 2018

Adv Healthcare Materials

View full text Add to dashboard Cite

Sepsis is characterized by systemic inflammatory response syndrome (SIRS) accompanied with infection. Gram-negative bacteria can evoke sepsis by activating the host immune system, such as the release of IL-6 and TNF-α, through their virulence factors. Outer membrane vesicles (OMVs), nanosized bilayered proteolipids derived from Gram-negative bacteria, harbor various virulence factors and are shown to induce SIRS. Here, drugs are repositioned to alleviate SIRS caused by Gram-negative bacterial OMVs. Using novel OMV-based drug screening systems, a total of 178 commercially available drugs are primarily screened, and a total of 18 repositioned drug candidates are found to effectively block IL-6 and TNF-α production from OMV-stimulated macrophages. After excluding the compounds which are previously known to intervene sepsis or which show cytotoxicity to macrophages, the compounds which show dose-dependency in inhibiting the release of IL-6 and TNF-α by the OMV-stimulated macrophages in vitro and which reduce OMV-induced SIRS in vivo are selected. Salbutamol, a β2 adrenergic receptor agonist, is selected as a novel candidate to alleviate OMV-induced SIRS. This study sheds light on using Gram-negative bacterial OMVs in exploring novel candidate compounds to alleviate inflammatory diseases including sepsis.

show abstract

The Agonists of Formyl Peptide Receptors Prevent Development of Severe Sepsis after Microbial Infection

Abstract: Material

Cited by 59 publications

References 56 publications

Airway Activation of Formyl Peptide Receptors Inhibits Th1 and Th17 Cell Responses via Inhibition of Mediator Release from Immune and Inflammatory Cells and Maturation of Dendritic Cells

Airway Activation of Formyl Peptide Receptors Inhibits Th1 and Th17 Cell Responses via Inhibition of Mediator Release from Immune and Inflammatory Cells and Maturation of Dendritic Cells

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

Drug Repositioning to Alleviate Systemic Inflammatory Response Syndrome Caused by Gram‐Negative Bacterial Outer Membrane Vesicles

Contact Info

Product

Resources

About