Effect of mite allergenic components on innate immune response: Synergy of protease (Group 1 &amp; 3) and non-protease (Group 2 &amp; 7) allergens

Yin, Sui-Chu; Liao, En-Chih; Ye, Chi-Xin; Chang, Ching-Yun; Tsai, Jaw‐Ji

doi:10.1016/j.imbio.2017.10.032

Cited by 14 publications

(7 citation statements)

References 15 publications

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“…These data corroborated that Tyr-p3-mediated PAR-2 mRNA induction in the stimulation of IL-8 and IL-1b production involves the signal transduction pathways via the MAP kinase ERK1/2 and p38 MAPK. Further, these findings are consistent with our previous reports indicating that the mite allergen-induced secretions of IL-6 or IL-8 were inhibited by MAPK and IkB inhibitors, suggesting that MAPK, p38 MAPK, and NFkB signaling pathways may be involved in mite-induced allergic airway inflammation (39,59). Studies have shown that the ERK and p38 MAP kinase signaling activation participates in the release of the inflammatory mediators, including IL-1b, TNF-a, and IL-8 (60,61).…”

Section: Discussionsupporting

confidence: 93%

“…The major allergens of T. putrescentiae are identified as Tyr-p2 and Tyr-p3, and both allergens may play an essential role in the pathogenesis of IgE-mediated allergic diseases in the storage mite-sensitive population ( 40 ). The protease allergenic component of house dust mite (Der p3) could activate human airway epithelium synergistically to increase the mRNA levels of IL-6 and IL-8 genes in the presence of non-protease allergenic component Der p2 ( 39 ). In this study, we demonstrated that there was an accumulative effect of rTyr-p2 in conjunction with nTyr-p3 on the stimulation of pro-inflammatory cytokine (IL-6 and IL-1β), chemokine (IL-8), and T helper-2 associated cytokine (IL-33) in PBMCs derived from allergic patients.…”

Section: Discussionmentioning

confidence: 99%

“…A suitable temperature cycle schedule for each PCR reaction was determined using an MJ Mini™ Personal Thermal Cycler (Bio-Rad, Foster, CA, USA). The primers of IL-6 and IL-8 were described in our previous study ( 39 ). Human ACTB (β-actin) was used as an internal control to normalize the levels of gene expression.…”

Section: Methodsmentioning

confidence: 99%

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Antagonism of Protease Activated Receptor-2 by GB88 Reduces Inflammation Triggered by Protease Allergen Tyr-p3

Wang

Tsai

et al. 2021

Front. Immunol.

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The occurrence of allergic diseases induced by aeroallergens has increased in the past decades. Among inhalant allergens, mites remain the important causal agent of allergic diseases. Storage mites- Tyrophagus putrescentiae are found in stored products or domestic environments. Major allergen Tyr-p3 plays a significant role in triggering IgE-mediated hypersensitivity. However, its effects on pulmonary inflammation, internalization, and activation in human epithelium remain elusive. Protease-activated receptors (PARs) are activated upon cleavage by proteases. A549 cells were used as an epithelial model to examine the PAR activation by Tyr-p3 and therapeutic potential of PAR-2 antagonist (GB88) in allergic responses. Enzymatic properties and allergen localization of Tyr-p3 were performed. The release of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK), and cell junction disruptions were evaluated after Tyr-p3 challenge. Enzymatic properties determined by substrate digestion and protease inhibitors indicated that Tyr-p3 processes a trypsin-like serine protease activity. The PAR-2 mRNA levels were significantly increased by nTyr-p3 but inhibited by protease inhibitors or GB88. Protease allergen of nTyr-p3 significantly increased the levels of pro-inflammatory cytokines (IL-6 and TNF-α), chemokine (IL-8), and IL-1β in epithelial cells. nTyr-p3 markedly increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and MAP kinase. When cells were pretreated with GB88 then added nTyr-p3, the phosphorylated ERK1/2 did not inhibit by GB88. GB88 increased ERK1/2 phosphorylation in human epithelium cells. GB88 is able to block PAR-2-mediated calcium signaling which inhibits the nTyr-p3-induced Ca2+ release. Among the pharmacologic inhibitors, the most effective inhibitor of the nTyr-p3 in the induction of IL-8 or IL-1β levels was GB88 followed by SBTI, MAPK/ERK, ERK, and p38 inhibitors. Levels of inflammatory mediators, including GM-CSF, VEGF, COX-2, TSLP, and IL-33 were reduced by treatment of GB88 or SBTI. Further, GB88 treatment down-regulated the nTyr-p3-induced PAR-2 expression in allergic patients with asthma or rhinitis. Tight junction and adherens junction were disrupted in epithelial cells by nTyr-p3 exposure; however, this effect was avoided by GB88. Immunostaining with frozen sections of the mite body showed the presence of Tyr-p3 throughout the intestinal digestive system, especially in the hindgut around the excretion site. In conclusion, our findings suggest that Tyr-p3 from domestic mites leads to disruption of the airway epithelial barrier after inhalation. Proteolytic activity of Tyr-p3 causes the PAR-2 mRNA expression, thus leading to the release of numerous inflammatory mediators. Antagonism of PAR2 activity suggests GB88 as the therapeutic potential for anti-inflammation medicine, especially in allergy development triggered by protease allergens.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Antagonism of Protease Activated Receptor-2 by GB88 Reduces Inflammation Triggered by Protease Allergen Tyr-p3

Wang

Tsai

et al. 2021

Front. Immunol.

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“…Many of these groups in HDM have been identified as having protease activity (groups 1, 3, 6, and 9). Group 1 HDM allergens exhibit cysteine protease activity, and are responsible for more than 50% of sensitization of HDM-allergic subjects [ 38 ]. Because our findings suggested that HDM-mediated BPIFA1 degradation is blocked by a pan cysteine protease inhibitor, E64D ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Degradation of bacterial permeability family member A1 (BPIFA1) by house dust mite (HDM) cysteine protease Der p 1 abrogates immune modulator function

Zhang

Trower

2020

International Journal of Biological Macromolecules

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Bacterial permeability family member A1 (BPIFA1) is one of the most abundant proteins present in normal airway surface liquid (ASL). It is known to be diminished in asthmatic patients' sputum, which causes airway hyperresponsiveness (AHR). What is currently unclear is how environmental factors, such as allergens' impact on BPIFA1's abundance and functions in the context of allergic asthma. House dust mite (HDM) is a predominant domestic source of aeroallergens. The group of proteases found in HDM is thought to cleave multiple cellular protective mechanisms, and therefore foster the development of allergic asthma. Here, we show that BPIFA1 is cleaved by HDM proteases in a time-, dose-, and temperature-dependent manner. We have also shown the main component in HDM that is responsible for BPIFA1's degradation is Der p1. Fragmented BPIFA1 failed to bind E . coli lipopolysaccharide (LPS), and hence elevated TNFα and IL-6 secretion in human whole blood. BPIFA1 degradation is also observed in vivo in bronchoalveolar fluid (BALF) of mice which are intranasally instilled with HDM. These data suggest that proteases associated with environmental allergens such as HDM cleave BPIFA1 and therefore impair its immune modulator function.

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“…However, new routes have started emerging in the field of research on the genesis and treatment of respiratory pathologies. The notion that non-hematopoietic tissues are a fundamental font of chemokines has been sustained by several experiments [ 174 ].…”

Section: Discussionmentioning

confidence: 99%

Alarmins and MicroRNAs, a New Axis in the Genesis of Respiratory Diseases: Possible Therapeutic Implications

Allegra

Murdaca

Gammeri

et al. 2023

IJMS

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It is well ascertained that airway inflammation has a key role in the genesis of numerous respiratory pathologies, including asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome. Pulmonary tissue inflammation and anti-inflammatory responses implicate an intricate relationship between local and infiltrating immune cells and structural pulmonary cells. Alarmins are endogenic proteins discharged after cell injury in the extracellular microenvironment. The purpose of our review is to highlight the alterations in respiratory diseases involving some alarmins, such as high mobility group box 1 (HMGB1) and interleukin (IL)-33, and their inter-relationships and relationships with genetic non-coding material, such as microRNAs. The role played by these alarmins in some pathophysiological processes confirms the existence of an axis composed of HMGB1 and IL-33. These alarmins have been implicated in ferroptosis, the onset of type 2 inflammation and airway alterations. Moreover, both factors can act on non-coding genetic material capable of modifying respiratory function. Finally, we present an outline of alarmins and RNA-based therapeutics that have been proposed to treat respiratory pathologies.

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Effect of mite allergenic components on innate immune response: Synergy of protease (Group 1 & 3) and non-protease (Group 2 & 7) allergens

Cited by 14 publications

References 15 publications

Antagonism of Protease Activated Receptor-2 by GB88 Reduces Inflammation Triggered by Protease Allergen Tyr-p3

Antagonism of Protease Activated Receptor-2 by GB88 Reduces Inflammation Triggered by Protease Allergen Tyr-p3

Degradation of bacterial permeability family member A1 (BPIFA1) by house dust mite (HDM) cysteine protease Der p 1 abrogates immune modulator function

Alarmins and MicroRNAs, a New Axis in the Genesis of Respiratory Diseases: Possible Therapeutic Implications

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