PMID- 32468025
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20210308
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 46
IP  - 2
DP  - 2020 Aug
TI  - Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses 
      through M2 polarization of macrophages.
PG  - 718-728
LID - 10.3892/ijmm.2020.4613 [doi]
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is an allergic immunological 
      response to Aspergillus fumigatus (Af) exposure, which induces a strong 
      T helper 2 (Th2) response via mechanisms that have yet to be elucidated. The aim 
      of the present study was to investigate the hypothesis that T2 ribonuclease from 
      Af (Af RNASET2) induces M2‑type macrophage polarization to produce a 
      T helper 2 (Th2) immune response. Recombinant Af RNASET2 (rAf RNASET2) was 
      expressed and purified in a prokaryotic pET system and BALB/c mice were immunized 
      with rAf RNASET2 for in vivo analyses. Expression levels of M2 polarization 
      factors were evaluated in RAW264.7 macrophages treated with rAf RNASET2 in vitro 
      using flow cytometry, reverse transcription‑quantitative PCR, and western blot 
      analysis. The results predicted that the mature Af RNASET2 protein (382 amino 
      acids; GenBank no. MN593022) contained two conserved amino acid sequence (CAS) 
      domains, termed CAS‑1 and CAS‑2, which are also characteristic of the RNASET2 
      family proteins. The protein expression levels of the Th2‑related cytokines 
      interleukin (IL)‑4, IL‑10, and IL‑13 were upregulated in mice immunized with 
      rAf RNASET2. RAW264.7 macrophages treated with rAf RNASET2 showed increased mRNA 
      expression levels of M2 factors [arginase 1, Il‑10, and Il‑13]; however, there 
      was no difference in cells treated with rAf RNASET2 that had been inactivated 
      with a ribonuclease inhibitor (RNasin). The protein expression levels of IL‑10 in 
      macrophage culture supernatant were also increased following stimulation with 
      rAf RNASET2. In addition, rAf RNASET2 upregulated the expression of 
      phosphorylated mitogen activated protein kinases (MAPKs) in RAW264.7 cells, 
      whereas MAPK inhibitors attenuated rAf RNASET2‑induced IL‑10 expression in 
      RAW264.7 cells. In conclusion, the present study reveals that high rAf RNASET2 
      activity is required for rAf RNASET2‑induced M2 polarization of macrophages and 
      suggests an important immune regulatory role for Af RNASET2 in ABPA pathogenesis.
FAU - Chen, Jia-Jie
AU  - Chen JJ
AD  - Department of Biochemistry and Molecular Biology, Health Science Center of 
      Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
FAU - He, Yong-Shen
AU  - He YS
AD  - Department of Biochemistry and Molecular Biology, Health Science Center of 
      Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
FAU - Zhong, Xiao-Jun
AU  - Zhong XJ
AD  - Central Laboratory, Shenzhen Nanshan Hospital, Shenzhen, Guangdong 518083, P.R. 
      China.
FAU - Cai, Ze-Lang
AU  - Cai ZL
AD  - Department of Biochemistry and Molecular Biology, Health Science Center of 
      Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
FAU - Lyu, Yan-Si
AU  - Lyu YS
AD  - Department of Dermatology, Shenzhen University General Hospital, Shenzhen, 
      Guangdong 518020, P.R. China.
FAU - Zhao, Zhen-Fu
AU  - Zhao ZF
AD  - Department of Biochemistry and Molecular Biology, Health Science Center of 
      Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
FAU - Ji, Kunmei
AU  - Ji K
AD  - Department of Biochemistry and Molecular Biology, Health Science Center of 
      Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200521
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Interleukin-13)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 3.1.- (Endoribonucleases)
RN  - EC 3.1.27.1 (ribonuclease T(2))
SB  - IM
MH  - Animals
MH  - Aspergillus fumigatus/*enzymology
MH  - Endoribonucleases/genetics/*metabolism
MH  - Female
MH  - Interleukin-10/metabolism
MH  - Interleukin-13/metabolism
MH  - Interleukin-4/metabolism
MH  - Macrophages/*cytology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - RAW 264.7 Cells
MH  - Th2 Cells/*cytology/immunology/*metabolism
PMC - PMC7307867
EDAT- 2020/05/30 06:00
MHDA- 2021/03/09 06:00
PMCR- 2020/05/21
CRDT- 2020/05/30 06:00
PHST- 2020/01/23 00:00 [received]
PHST- 2020/04/09 00:00 [accepted]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
PHST- 2020/05/21 00:00 [pmc-release]
AID - ijmm-46-02-0718 [pii]
AID - 10.3892/ijmm.2020.4613 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Aug;46(2):718-728. doi: 10.3892/ijmm.2020.4613. Epub 2020 May 
      21.