PMID- 31185757 OWN - NLM STAT- MEDLINE DCOM- 20200220 LR - 20200220 IS - 1532-4311 (Electronic) IS - 0882-0139 (Linking) VI - 48 IP - 8 DP - 2019 Nov TI - Disturbed Transcription of TLRs' Negative Regulators and Cytokines Secretion among TLR4- and 9-Activated PBMCs of Agammaglobulinemic Patients. PG - 860-874 LID - 10.1080/08820139.2019.1604742 [doi] AB - Toll-like receptors (TLRs) are inevitable elements for immunity development and antibody production. TLRs are in close interaction with Bruton's tyrosine kinase which has been found mutated and malfunctioned in the prototype antibody deficiency disease named X-linked agammaglobulinemia (XLA). TLRs' ability was evaluated to induce transcription of TLR-negative regulators, including suppressor of cytokine signaling 1 (SOCS1), interleukin-1 receptor-associated kinase 3 (IRAK-M), tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20), and Ring finger protein 216 (RNF216), and Tumor necrosis factor-alpha (TNF-alpha) and Interferon-alpha (IFN-alpha) production via Lipopolysaccharides (LPS) and CpG-A oligodeoxynucleotides (CpG-A ODN). Measured by TaqMan real-time polymerase chain reaction (PCR), meaningfully increased transcripts of SOCS1 and RNF216 were found in XLA peripheral blood mononuclear cells (PBMCs). Also, TLR inductions of XLA have led to similar downregulations in the regulator's transcription which was different from that in healthy donors. Cytokine measurement by enzyme-linked immunosorbent assay (ELISA) revealed a significant lower TNF-alpha production both before and after LPS. By selected molecules in this study, TLRs' potential defectiveness range expands TLRs expression, downstream signaling, and cytokine production. The results show new potential elements that could play a part in TLRs defect and pathogenesis of agammaglobulinemia as well. FAU - Sanaei, Roozbeh AU - Sanaei R AUID- ORCID: 0000-0002-1055-9305 AD - Immunology Research Center (IRC), Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences , Tehran , Iran. AD - Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN) , Tehran , Iran. FAU - Rezaei, Nima AU - Rezaei N AD - Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN) , Tehran , Iran. AD - Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran. AD - Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN) , Tehran , Iran. FAU - Aghamohammadi, Asghar AU - Aghamohammadi A AD - Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran. FAU - Delbandi, Ali-Akbar AU - Delbandi AA AD - Immunology Research Center (IRC), Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences , Tehran , Iran. AD - Department of Immunology, School of Medicine, Iran University of Medical Sciences , Tehran , Iran. FAU - Tavasolian, Parsova AU - Tavasolian P AD - Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran. FAU - Tajik, Nader AU - Tajik N AD - Immunology Research Center (IRC), Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences , Tehran , Iran. AD - Department of Immunology, School of Medicine, Iran University of Medical Sciences , Tehran , Iran. LA - eng PT - Journal Article DEP - 20190611 PL - England TA - Immunol Invest JT - Immunological investigations JID - 8504629 RN - 0 (CPG-oligonucleotide) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (SOCS1 protein, human) RN - 0 (Suppressor of Cytokine Signaling 1 Protein) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptor 9) RN - 0 (Toll-Like Receptors) RN - EC 2.3.2.27 (RNF216 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.11.1 (IRAK3 protein, human) RN - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases) RN - EC 3.4.19.12 (TNFAIP3 protein, human) RN - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3) SB - IM MH - Adolescent MH - Agammaglobulinemia/blood/genetics/*metabolism MH - Cells, Cultured MH - Child MH - Cytokines/*metabolism MH - Humans MH - Interleukin-1 Receptor-Associated Kinases/genetics/metabolism MH - Leukocytes, Mononuclear/drug effects/*metabolism MH - Lipopolysaccharides/pharmacology MH - Male MH - Oligodeoxyribonucleotides/pharmacology MH - Suppressor of Cytokine Signaling 1 Protein/genetics/metabolism MH - Toll-Like Receptor 4/genetics/*metabolism MH - Toll-Like Receptor 9/genetics/*metabolism MH - Toll-Like Receptors/genetics/*metabolism MH - Transcription, Genetic/drug effects MH - Tumor Necrosis Factor alpha-Induced Protein 3/genetics/metabolism MH - Ubiquitin-Protein Ligases/genetics/metabolism MH - Young Adult OTO - NOTNLM OT - Agammaglobulinemic OT - BTK OT - IRAK-M OT - RNF216 OT - SOCS1 OT - TLR OT - TNFAIP3 OT - XLA EDAT- 2019/06/13 06:00 MHDA- 2020/02/23 06:00 CRDT- 2019/06/13 06:00 PHST- 2019/06/13 06:00 [pubmed] PHST- 2020/02/23 06:00 [medline] PHST- 2019/06/13 06:00 [entrez] AID - 10.1080/08820139.2019.1604742 [doi] PST - ppublish SO - Immunol Invest. 2019 Nov;48(8):860-874. doi: 10.1080/08820139.2019.1604742. Epub 2019 Jun 11.