The Role of Heat Shock Protein 70 kDa in Asthma

Figures & data

Table 1 HSP70 Allergens of Different Species

HSP70 Allergens	Species	References
Alt a 3	Alternaria alternate (mold)	Breitenbach & Simon-Nobbe 2002^Citation113
Pen c 19	Penicillium citrinum (mold)	Shen et al 1997^Citation114
Mala s 10	Malassezia sympodialis (skin colonizing yeast)	Andersson et al 2004^Citation20
Der f 28	Dermatophagoides farina (American house dust mite)	Aki et al 1994;^Citation115 An et al 2013^Citation116
Der p 28	Dermatophagoides pteronyssinus (European house dust mite)	Liu et al 2018^Citation117
Tyr p 28	Tyrophagus putrescentiae (mold mite)	Cui et al 2016^Citation118
Cor a 10	Corylus avellana (European hazel)	Gruehn et al 2003^Citation119
Aed a 8	Aedes aegypti (yellow fever mosquito)	Cantillo et al 2017^Citation15
Cla h Hsp70	Cladosporium herbarum (mold)	Breitenbach & Simon-Nobbe 2002;^Citation113 Zhang et al 1996^Citation120
Blo t Mag29	Blomia tropicalis (dust mite)	Simon-Nobbe et al 2008^Citation121

Note: In accordance with the database AllFam (http://www.meduniwien.ac.at/allfam/).¹⁶

Figure 1 HSP70 prevents neutrophil hyperactivation at the site of inflammation. Production of reactive oxygen species (ROS) is one mechanism of neutrophil defense against pathogens; however, the trigger of ROS production can also cause damage to host tissues or damage-associated molecular patterns (DAMPS). ATP is known to stimulate ROS production. Uncontrolled ROS production leads to NETosis and inflammation progression. HSP70, as an ATPase, can dephosphorylate ATP to ADP, which is less pyrogenic than ATP, and thus prevent uncontrolled ROS production. Moreover, HSP70 was involved in switching from necrosis and NETosis of neutrophils to apoptosis. Apoptosis and efferocytosis of apoptotic neutrophils are associated with inflammation resolution.

Figure 2 HSP70 induces neutrophil recruitment to the site of inflammation. Exogenous substance challenge induces neutrophil recruitment to the airways. However, inhaled allergen promotes IL-4 production by ILC2, and further by DC-activated Th2 cells. IL-4 concentration is increased locally and systemically. IL-4 blocks neutrophil recruitment, which promotes the recruitment of eosinophils and stimulates allergic airway inflammation. HSP70 activates the production of IL-1β and IL-8 by epithelial cells, which attract neutrophils to the periphery. Neutrophils block Th2 proliferation and allergic airway inflammation. HSP70 also prevents DC maturation and induces IL-10 production.

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