Mechanism Research For TREM-1 Involved Ovalbum-Ininduced Allergic Asthmatic Responses In Mice

Allergic asthma has become one of the world’s most common diseases,and around 300 million people are under sufferings of this uncomfortable chronic respiratory inflammation globally,while China owns 10% of this figure.However,the total number of the patients is still rising rapidly owing to the fast industrialization and air pollutions.Nevertheless,current studies for the roles of TREM-1 in asthmatic symptoms is still not so well-known,and deeper research for new therapeutic targets is promising both theoretically and realistically in the future.TREM-1(Triggering receptor expressed on myeloid cells 1)belongs to a protein family which is widely expressed on the surface of immune cells and plays a key role in regulating many essential inflammation reactions.TREMs have been identified to be involved with a large number of non-infectious inflammatory diseases,such as the occurrences of arthritis,COPD(chronic obstructive pulmonary disease),allergic asthma,inflammatory bowel disease and acute pancreatitis,etc.This project covers the main two parts,the one is detailed research into the functions for TREM-1 and its ligands in wildtype asthmatic mice,in order to make a primary judgement whether TREM-1 influences asthmatic symptoms by interventions of its signaling pathway;and the other one is further confirmations for these primary decisions by employing TREM-1 knockout asthmatic models via CRISPR-Cas9 genetic edition techniques,and both fields cover the stimulation and inhibition processings.Through the above two major parts of research,some important phenomena have been drawn:1.TREM-1 expression level has been apparently increased by 8.17-fold in mice asthmatic tissues(P < 0.01),and its ligands share the same trends as well(P < 0.05),which indicates that TREM-1 signaling might be related to allergic asthma occurrence;2.Stimulations of TREM-1 signaling via CD177 and PGLYRP1 recombinant proteins on wildtype asthmatic mice could result in correspondent inflammatory reactions,including more thickened airway walls and worse inflammatory cell infiltration conditions,high priorities of inflammatory cell percentages(P < 0.01).as well as their molecular expressions under TREM-1 regulations;3.Blockage of TREM-1 signaling by LP17 and TREM-1/fc fusion protein in wildtype could return the weakened pulmonary functions.Airway thickenings and inflammatory cell infiltration situations returned to normal as well.Meanwhile,leukocyte classification in the bronchoalveolar lavage fluid(BALF)also went back to normal(P < 0.01).In addition,TLR1 and TLR6 containing levels were observed to be significantly enhanced(P < 0.01)through the expression analysis of Toll-like receptors in the lung tissues,and the downstream cytokine IL-1β was also discovered to share the same trend(P < 0.05).However,these three effectors were obviously down-regulated(P < 0.05)when treated with LP17;4.Through the ovalbumin-induced asthmatic reactions in TREM-1 knockout mice,improved tolerance of the allergen has been discovered in the knockout group,and the inflammatory effects get much relieved(P < 0.05),such as better pulmonary functions,improved leukocyte classifications in the BALF,and weakened conditions of airway thickening and EOS filtrations compared with the asthmatic groups in the wildtype.Furthermore,IL-1β expression level was identified to be dramatically inhibited in the TREM-1 knockout groups(P < 0.05)via RT-PCR assay,which is essential in amplifying inflammatory processes.Above research all suggest that TREM-1 might be playing an important role in regulating asthma happenings,but the underlying mechanisms still need further explorations,which might help provide a novel molecular targeted therapy strategy in the future’s asthma clinical treatment.