Context: Type I hypersensitivity affects approximately one-third of the global population. As the pathophysiology underlying the development of type I hypersensitivity (asthma, food allergy, and anaphylactic shock, etc.) is complex and heterogeneous, animal model studies continue to be the key to identifying novel molecular pathways and providing therapeutic strategies.Objective: Selection of the animal model should be done with careful consideration of the protocol variables, animal species, and strains to accurately reflect the clinical symptoms typical of humans.Methods: The following databases were searched: PubMed and Web of Science.Results and conclusion: Foreign allergens include allergenic proteins and chemical haptens. This review summarizes the various methods used for designing animal models of common allergenic protein-induced type I hypersensitivity, namely, passive anaphylaxis model, active systemic anaphylaxis/anaphylaxis shock model, food allergy model, asthma model, and IgE-mediated cell models. Additionally, we summarize shrimp tropomyosin-induced type I hypersensitivity models from our previous studies and discuss their advantages and limitations compared with that of ovalbumin-induced models.

Background. Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of Abelmoschus manihot (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. Methods. Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance. Results. LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF-α and IL-6 in RAW 264.7 cells. Conclusions. These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.

Original Article Deletion of the miR-144/451 cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis Fan Wu, Xiaoling Yuan, Weili Liu, Lijun Meng, Xiuru Li, Xiang Gao, Shuting Zhou, Lei Fang, Duonan Yu

Background: Ovalbumin (OVA) and house dust mite (HDM) are widely used allergenic proteins in murine models of allergic asthma. In our previous studies, shrimp tropomyosin (ST) was shown to induce type I hypersensitivity, including asthma-like responses. Here, we compared airway eosinophilic inflammation models induced by OVA, HDM, or ST using a protocol of three intraperitoneal (i.p.) sensitizations followed by a single intratracheal (i.t.) allergen challenge.Methods: C57BL/6J mice were sensitized via three i.p. injections of OVA, HDM, or ST mixed with Al(OH)₃, followed by a single i.t. challenge with the respective allergen. Lung transcriptomic analysis, plasma IgE levels, bronchoalveolar lavage (BAL) fluid cell counts, cytokine and chemokine mRNA levels, and histopathological assessments were performed to evaluate airway inflammation.Results: A single i.t. challenge with ST or HDM significantly increased the lung-to-body weight ratio, eosinophil infiltration, and mucus hypersecretion, accompanied by elevated mRNA levels of Th2 cytokines (Il-4, Il-5, Il-13) and increased the total cell count and eosinophil count in the BAL fluid. In contrast, OVA induced only mild eosinophilic inflammation, suggesting that repeated exposures may be required to elicit a robust allergic response. RNA sequencing and qRT-PCR further identified key chemokines associated with eosinophil recruitment (Ccl-11, Ccl-24), Th2 polarization (Ccl-17), and neutrophil activation (Cxcl-1).Conclusion: A single i.t. challenge of ST, similar to HDM, exhibits a potent ability to induce eosinophilic inflammation and Th2-type immune responses in a murine model of allergic asthma, surpassing the effects of OVA.

miR-144/451 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulate two antioxidative systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether these two genes coordinate to affect ROS scavenging and the anemic phenotype, or which gene is more important for recovery from acute anemia, has not been explored. To address these questions, we crossed miR-144/451 knockout (KO) and Nrf2 KO mice and examined the phenotype change in the animals as well as the ROS levels in erythroid cells either at baseline or under stress condition. Several discoveries were made in this study. First, Nrf2/miR-144/451 double-KO mice unexpectedly exhibit similar anemic phenotypes as miR-144/451 single-KO mice during stable erythropoiesis, although compound mutations of miR-144/451 and Nrf2 lead to higher ROS levels in erythrocytes than single gene mutations. Second, Nrf2/miR-144/451 double-mutant mice exhibit more dramatic reticulocytosis than miR-144/451 or Nrf2 single-KO mice during days 3 to 7 after inducing acute hemolytic anemia using phenylhydrazine (PHZ), indicating a synergistic effect of miR-144/451 and Nrf2 on PHZ-induced stress erythropoiesis. However, the coordination does not persist during the whole recovery stage of PHZ-induced anemia; instead, Nrf2/miR-144/451 double-KO mice follow a recovery pattern similar to miR-144/451 single-KO mice during the remaining period of erythropoiesis. Third, the complete recovery from PHZ-induced acute anemia in miR-144/451 KO mice takes longer than in Nrf2 KO mice. Our findings demonstrate that complicated crosstalk between miR-144/451 and Nrf2 does exist and the crosstalk of these two antioxidant systems is development-stage-dependent. Our findings also demonstrate that miRNA deficiency could result in a more profound defect of erythropoiesis than dysfunctional transcription factors.