PMID- 38531465
OWN - NLM
STAT- MEDLINE
DCOM- 20240504
LR  - 20240508
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1833
DP  - 2024 Jun 15
TI  - IL-6 mediates olfactory dysfunction in a mouse model of allergic rhinitis.
PG  - 148885
LID - S0006-8993(24)00139-2 [pii]
LID - 10.1016/j.brainres.2024.148885 [doi]
AB  - BACKGROUND: Immune-inflammatory response is a key element in the occurrence and 
      development of olfactory dysfunction (OD) in patients with allergic rhinitis 
      (AR). As one of the core factors in immune-inflammatory responses, interleukin 
      (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also 
      play an important role in OD induced by diseases, such as Sjogren's syndrome and 
      coronavirus disease 2019. However, there is no study has reported its role in OD 
      in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, 
      in an attempt to discover a new target for the prevention and treatment of OD in 
      patients with AR. METHODS: Differential expression analysis was performed using 
      the public datasets GSE52804 and GSE140454 for AR, and differentially expressed 
      genes (DEGs) were obtained by obtaining the intersection points between these two 
      datasets. IL-6, a common differential factor, was obtained by intersecting the 
      DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR 
      mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the 
      reliability of IL-6 as a key factor of OD in AR and explore the potential 
      mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal 
      mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 
      was established to identify the cellular and molecular mechanisms of 
      IL-6-mediated OD in AR. RESULTS: The level of IL-6 in the nasal mucosa and 
      olfactory bulb of AR mice with OD significantly increased and showed a positive 
      correlation with the expression of olfactory bulb microglia marker Iba-1 and the 
      severity of OD. In-vitro experiments showed that the level of IL-6 significantly 
      increased in the supernatant after the nasal mucosa epithelial cells were 
      stimulated by Derp1, along with significantly decreased barrier function of the 
      nasal mucosa. The expression levels of neuroinflammatory markers IL-1beta and INOS 
      increased after a conditioned culture of microglia with the supernatant including 
      IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the 
      expression of IL-1beta and INOS significantly diminished. CONCLUSION: IL-6 plays a 
      key role in the occurrence and development of OD in AR, which may be related to 
      its effect on olfactory bulb microglia-mediated neuroinflammation.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Song, Xiao-Yu
AU  - Song XY
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China.
FAU - Sun, Qi
AU  - Sun Q
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China.
FAU - Wei, Shi-Zhuang
AU  - Wei SZ
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China.
FAU - Wang, Han-Rui
AU  - Wang HR
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China.
FAU - Wang, Yao
AU  - Wang Y
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China.
FAU - Zhang, Wen-Bin
AU  - Zhang WB
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China.
FAU - Ren, Chao
AU  - Ren C
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China. Electronic address: renchaotg@126.com.
FAU - Song, Xi-Cheng
AU  - Song XC
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China. Electronic address: drxchsong@163.com.
FAU - Mou, Ya-Kui
AU  - Mou YK
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding 
      Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical 
      Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, 
      Yantai, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 
      Yuhuangding Hospital, Yantai, China. Electronic address: muykmd@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240324
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Interleukin-6)
RN  - 0 (interleukin-6, mouse)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Disease Models, Animal
MH  - *Interleukin-6/metabolism
MH  - Microglia/metabolism
MH  - *Olfaction Disorders/metabolism
MH  - Olfactory Bulb/metabolism
MH  - Ovalbumin
MH  - *Rhinitis, Allergic/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
OTO - NOTNLM
OT  - Allergic rhinitis
OT  - Interleukin-6 (IL-6)
OT  - Microglia
OT  - Olfactory bulb
OT  - Olfactory dysfunction
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/03/27 00:44
MHDA- 2024/05/05 07:47
CRDT- 2024/03/26 20:16
PHST- 2023/04/12 00:00 [received]
PHST- 2024/03/07 00:00 [revised]
PHST- 2024/03/21 00:00 [accepted]
PHST- 2024/05/05 07:47 [medline]
PHST- 2024/03/27 00:44 [pubmed]
PHST- 2024/03/26 20:16 [entrez]
AID - S0006-8993(24)00139-2 [pii]
AID - 10.1016/j.brainres.2024.148885 [doi]
PST - ppublish
SO  - Brain Res. 2024 Jun 15;1833:148885. doi: 10.1016/j.brainres.2024.148885. Epub 
      2024 Mar 24.