Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs

Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some...

Full description

Saved in:
Bibliographic Details
Main Authors: Elias A. Said, Sumaya Al-Dughaishi, Wadha Al-Hatmi, Iman Al-Reesi, Mohammed S. Al-Balushi, Atika Al-Bimani, Juma Z. Al-Busaidi, Marwa Al-Riyami, Murtadha Al-Khabori, Salam Al-Kindi, Francesco A. Procopio, Shadia Al-Sinawi, Aliyaa Al-Ansari, Crystal Y. Koh, Khalid Al-Naamani, Ali A. Al-Jabri
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2023/7944102
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832553060907352064
author Elias A. Said
Sumaya Al-Dughaishi
Wadha Al-Hatmi
Iman Al-Reesi
Mohammed S. Al-Balushi
Atika Al-Bimani
Juma Z. Al-Busaidi
Marwa Al-Riyami
Murtadha Al-Khabori
Salam Al-Kindi
Francesco A. Procopio
Shadia Al-Sinawi
Aliyaa Al-Ansari
Crystal Y. Koh
Khalid Al-Naamani
Ali A. Al-Jabri
author_facet Elias A. Said
Sumaya Al-Dughaishi
Wadha Al-Hatmi
Iman Al-Reesi
Mohammed S. Al-Balushi
Atika Al-Bimani
Juma Z. Al-Busaidi
Marwa Al-Riyami
Murtadha Al-Khabori
Salam Al-Kindi
Francesco A. Procopio
Shadia Al-Sinawi
Aliyaa Al-Ansari
Crystal Y. Koh
Khalid Al-Naamani
Ali A. Al-Jabri
author_sort Elias A. Said
collection DOAJ
description Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p<0.01). IAPCs produced more PTN than MK (p<0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p<0.05) and in MDDCs by TLRs 7/8 (p<0.05). TLR4 induced a stronger MK production than NAS TLRs (p≤0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p<0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.
format Article
id doaj-art-63d42028829e48bd92955fde7b1e7f60
institution Kabale University
issn 2314-7156
language English
publishDate 2023-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-63d42028829e48bd92955fde7b1e7f602025-02-03T05:57:00ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/7944102Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRsElias A. Said0Sumaya Al-Dughaishi1Wadha Al-Hatmi2Iman Al-Reesi3Mohammed S. Al-Balushi4Atika Al-Bimani5Juma Z. Al-Busaidi6Marwa Al-Riyami7Murtadha Al-Khabori8Salam Al-Kindi9Francesco A. Procopio10Shadia Al-Sinawi11Aliyaa Al-Ansari12Crystal Y. Koh13Khalid Al-Naamani14Ali A. Al-Jabri15Department of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of Microbiology and ImmunologyDepartment of PathologyDepartment of HematologyDepartment of HematologyService of Immunology and AllergyDepartment of PathologyDepartment of BiologyDepartment of Microbiology and ImmunologyDepartment of MedicineDepartment of Microbiology and ImmunologyMidkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p<0.01). IAPCs produced more PTN than MK (p<0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p<0.05) and in MDDCs by TLRs 7/8 (p<0.05). TLR4 induced a stronger MK production than NAS TLRs (p≤0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p<0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.http://dx.doi.org/10.1155/2023/7944102
spellingShingle Elias A. Said
Sumaya Al-Dughaishi
Wadha Al-Hatmi
Iman Al-Reesi
Mohammed S. Al-Balushi
Atika Al-Bimani
Juma Z. Al-Busaidi
Marwa Al-Riyami
Murtadha Al-Khabori
Salam Al-Kindi
Francesco A. Procopio
Shadia Al-Sinawi
Aliyaa Al-Ansari
Crystal Y. Koh
Khalid Al-Naamani
Ali A. Al-Jabri
Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
Journal of Immunology Research
title Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
title_full Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
title_fullStr Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
title_full_unstemmed Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
title_short Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs
title_sort differential production of midkine and pleiotrophin by innate apcs upon stimulation through nucleic acid sensing tlrs
url http://dx.doi.org/10.1155/2023/7944102
work_keys_str_mv AT eliasasaid differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT sumayaaldughaishi differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT wadhaalhatmi differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT imanalreesi differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT mohammedsalbalushi differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT atikaalbimani differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT jumazalbusaidi differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT marwaalriyami differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT murtadhaalkhabori differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT salamalkindi differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT francescoaprocopio differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT shadiaalsinawi differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT aliyaaalansari differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT crystalykoh differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT khalidalnaamani differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs
AT aliaaljabri differentialproductionofmidkineandpleiotrophinbyinnateapcsuponstimulationthroughnucleicacidsensingtlrs