J Rhinol.  2023 Nov;30(3):135-138. 10.18787/jr.2023.00042.

Extracellular Hsp70 Is Involved in the CXCL12/CXCR4 Pathway in Primary Human Nasal Epithelial Cells: A Preliminary Study

• Kim SH
• Kahng DY
• Kim KS
• Min HJ

• KMID: 2548189
• DOI: http://doi.org/10.18787/jr.2023.00042

Abstract

Background and Objectives
To date, no studies have been conducted on the interaction between extracellular heat shock protein 70 (Hsp70) and C-X-C chemokine receptor type 4 (CXCR4) in the upper airway. We aimed to evaluate the relationship between extracellular Hsp70 and CXCR4 and their role in the primary human nasal epithelium.
Methods
We cultured primary human nasal epithelial (HNE) cells in an air–liquid interface. Macrogen performed single-cell quantitative polymerase chain reaction and sequencing. We conducted western blot analysis for the CXCR4 and mitogen-activated protein kinase (MAPK) pathways.
Results
Extracellular Hsp70 treatment significantly increased the genetic expression and protein levels of CXCR4 in primary HNE cells. Phospho-ERK expression was increased by cotreatment with Hsp70 and CXCL12, but inhibited by pretreatment with AMD3100, a CXCR4 inhibitor. Pretreatment with an anti-Hsp70 antibody reduced phospho-ERK expression upregulation induced by cotreatment with Hsp70 and CXCL12.
Conclusion
Extracellular Hsp70 participates in the activation of the CXCR4-dependent downstream signaling pathway in HNE cells. Further studies should evaluate the extracellular Hsp70-CXCL12/CXCR4 axis and the role of its components in the development of inflammatory diseases.

Keyword

Hsp70; CXCL12; CXCR4; Nasal epithelium

Figure

• 

  Fig. 1. Administration of extracellular Hsp70 upregulated the expression of CXCR4 in primary HNE cells. A: Western blot showing the increased CXCR4 expression after Hsp70 treatment. B: Fold change in CXCR4 expression after Hsp70 treatment. HNE, human nasal epithelial. *p<0.05.

• 

  Fig. 2. Activation of the CXCL12/CXCR4 pathway by extracellular Hsp70 in primary HNE cells. A: p-ERK signaling was upregulated after cotreatment with Hsp70 and CXCL12, as revealed by western blotting. B: Pretreatment with an anti-Hsp70 antibody decreased the upregulation of p-ERK expression induced by cotreatment with Hsp70 and CXCL12, as demonstrated by western blotting. HNE, human nasal epithelial.

Reference

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