Antimicrobial peptide LL-37 increases rhinovirus-induced interferon β expression in human airway epithelial cells through a Ca2+-dependent mechanism
(2025) In Biochemistry and Biophysics Reports 43.- Abstract
- The human cathelicidin LL-37 is active against both bacteria and viruses, but it also shows immunomodulatory properties. Here, we assess the impact of LL-37 on viral signaling in human airway epithelial BEAS-2B cells infected with the respiratory pathogen rhinovirus (RV). We show that LL-37 (4 μM) enhances RV-induced expression of interferon β (IFNβ) transcript and reduces viral-load. LL-37-evoked potentiation of RV-stimulated IFNβ does not involve up-regulation of the classical viral TLR3, MDA5 and RIG-I receptors. Moreover, the LL-37-induced stimulation of IFNβ expression in the presence of RV is abolished by chloroquine, an inhibitor of endosomal acidification. Interestingly, RV + LL-37-induced stimulation of IFNβ is observed in the... (More)
- The human cathelicidin LL-37 is active against both bacteria and viruses, but it also shows immunomodulatory properties. Here, we assess the impact of LL-37 on viral signaling in human airway epithelial BEAS-2B cells infected with the respiratory pathogen rhinovirus (RV). We show that LL-37 (4 μM) enhances RV-induced expression of interferon β (IFNβ) transcript and reduces viral-load. LL-37-evoked potentiation of RV-stimulated IFNβ does not involve up-regulation of the classical viral TLR3, MDA5 and RIG-I receptors. Moreover, the LL-37-induced stimulation of IFNβ expression in the presence of RV is abolished by chloroquine, an inhibitor of endosomal acidification. Interestingly, RV + LL-37-induced stimulation of IFNβ is observed in the absence but not in the presence of the Ca2+ chelating agent EGTA, indicating that Ca2+ is critical for this effect. Indeed, we demonstrate that LL-37 increases intracellular [Ca2+] in cells loaded with the fluorescent Ca2+ indicator Fluo-4 AM. Furthermore, we reveal that treatment with RV in combination with the Ca2+ ionophore A23187 promotes IFNβ expression, showing the importance of Ca2+. In conclusion, we demonstrate that LL-37 acts in synergy with RV to enhance IFNβ expression and that this effect involves LL-37-induced increase in intracellular [Ca2+]. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3a3ebe4f-d129-4971-b993-dcc5fb6640cb
- author
- Cerps, Samuel
LU
; Ramu, Sangeetha
LU
; Gidlöf, Olof
LU
; Menzel, Mandy
LU
; Swärd, Karl
LU
; Uller, Lena
LU
and Nilsson, Bengt-Olof
LU
- organization
-
- Respiratory Immunopharmacology (research group)
- Cardiovascular Epigenetics (research group)
- Molecular Cardiology (research group)
- Molecular Epidemiology and Cardiology (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- LTH Profile Area: Aerosols
- Cellular Biomechanics (research group)
- LU Profile Area: Proactive Ageing
- Vascular Physiology (research group)
- publishing date
- 2025-09-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemistry and Biophysics Reports
- volume
- 43
- article number
- 102105
- publisher
- Elsevier
- external identifiers
-
- pmid:40612001
- scopus:105008547651
- ISSN
- 2405-5808
- DOI
- 10.1016/j.bbrep.2025.102105
- language
- English
- LU publication?
- yes
- id
- 3a3ebe4f-d129-4971-b993-dcc5fb6640cb
- alternative location
- https://linkinghub.elsevier.com/retrieve/pii/S240558082500192X
- date added to LUP
- 2025-07-29 08:54:55
- date last changed
- 2025-07-30 04:02:42
@article{3a3ebe4f-d129-4971-b993-dcc5fb6640cb, abstract = {{The human cathelicidin LL-37 is active against both bacteria and viruses, but it also shows immunomodulatory properties. Here, we assess the impact of LL-37 on viral signaling in human airway epithelial BEAS-2B cells infected with the respiratory pathogen rhinovirus (RV). We show that LL-37 (4 μM) enhances RV-induced expression of interferon β (IFNβ) transcript and reduces viral-load. LL-37-evoked potentiation of RV-stimulated IFNβ does not involve up-regulation of the classical viral TLR3, MDA5 and RIG-I receptors. Moreover, the LL-37-induced stimulation of IFNβ expression in the presence of RV is abolished by chloroquine, an inhibitor of endosomal acidification. Interestingly, RV + LL-37-induced stimulation of IFNβ is observed in the absence but not in the presence of the Ca2+ chelating agent EGTA, indicating that Ca2+ is critical for this effect. Indeed, we demonstrate that LL-37 increases intracellular [Ca2+] in cells loaded with the fluorescent Ca2+ indicator Fluo-4 AM. Furthermore, we reveal that treatment with RV in combination with the Ca2+ ionophore A23187 promotes IFNβ expression, showing the importance of Ca2+. In conclusion, we demonstrate that LL-37 acts in synergy with RV to enhance IFNβ expression and that this effect involves LL-37-induced increase in intracellular [Ca2+].}}, author = {{Cerps, Samuel and Ramu, Sangeetha and Gidlöf, Olof and Menzel, Mandy and Swärd, Karl and Uller, Lena and Nilsson, Bengt-Olof}}, issn = {{2405-5808}}, language = {{eng}}, month = {{09}}, publisher = {{Elsevier}}, series = {{Biochemistry and Biophysics Reports}}, title = {{Antimicrobial peptide LL-37 increases rhinovirus-induced interferon β expression in human airway epithelial cells through a Ca2+-dependent mechanism}}, url = {{http://dx.doi.org/10.1016/j.bbrep.2025.102105}}, doi = {{10.1016/j.bbrep.2025.102105}}, volume = {{43}}, year = {{2025}}, }