Asthma is a chronic inflammatory disease of the airway characterized by variable airflow obstruction and bronchial hyper-responsiveness. In addition, patients with asthma have been reported that high prevalence of dental caries and gingivitis, which are induced by low salivation due to the medication for asthma. However, it is not known that asthma related allergens such as house dust mite (HDM) and German cockroach extract (GCE) have direct effects on the generation of gingival inflammation. HDM and GCE proteases are potent inducers proinflammatory cytokines through protease-activated receptor (PAR). Toll like receptor (TLR) family as the major receptor for endotoxin from GCE and HDM. Furthermore, the NLR family, pyridine domain-containing 3 (NLRP3) inflammasome is activated by a wide rage of danger signals. In the present study, we investigated the level of NLRP3 inflammasone, interlukin-8 (IL-8), IL-6 and IL-1β mRNA expression and the characteristics of Ca2+signal by GCE and HDM in the human gingival epithelial cells. HDM and GCE induced increases in NLRP3 and proinflammatory cytokines mRNA expression level and intracellular concentration of Ca2+ ([Ca2+]i), respectively. Endotoxin-free GCE activated PAR2, but endotoxin-free HDM did not activate any PARs. In human gingival epithelial cells, whereas lipopolisacaride, a Gram-negative endotoxin, did not induce Ca2+ signal, HDM and GCE containing endotoxins induced Ca2+ signal from thapsigargin (Tg), an inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase, -sensitive Ca2+ stores via phospholipase C (PLC)/inositol 1, 4, 5-trisphosphate (IP3) pathway. These results suggest that asthma related allergens induce Ca2+ signaling and cytokine release in human gingival epithelial cells.