Home LiteratureArticle Details
PMID: 19161415 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms.

Immunological reviews ·Vol. 226 ·2008-12-00 ·Pages 41-56

Hu X, Chakravarty SD, Ivashkiv LB

Abstract

Activated macrophages and their inflammatory products play a key role in innate immunity and in pathogenesis of autoimmune/inflammatory diseases. Macrophage activation needs to be tightly regulated to rapidly mount responses to infectious challenges but to avoid toxicity associated with excessive activation. Rapid and potent macrophage activation is driven by cytokine-mediated feedforward loops, while excessive activation is prevented by feedback inhibition. Here we discuss feedforward mechanisms that augment macrophage responses to Toll-like receptor (TLR) ligands and cytokines that are mediated by signal transducer and activator of transcription 1 (STAT1) and induced by interferon-gamma (IFN-gamma). IFN-gamma also drives full macrophage activation by inactivating feedback inhibitory mechanisms, such as those mediated by interleukin-10 (IL-10), and STAT3. Priming of macrophages with IFN-gamma reprograms cellular responses to other cytokines, such as type I IFNs and IL-10, with a shift toward pro-inflammatory STAT1-dominated responses. Similar but partially distinct priming effects are induced by other cytokines that activate STAT1, including type I IFNs and IL-27. We propose a model whereby opposing feedforward and feedback inhibition loops crossregulate each other to fine tune macrophage activation. In addition, we discuss how dysregulation of the balance between feedforward and feedback inhibitory mechanisms can contribute to the pathogenesis of autoimmune and inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus.

MeSH Terms
Animals Feedback, Physiological/immunology Humans Interferons/immunology,metabolism Interleukin-10/immunology,metabolism Macrophage Activation/immunology STAT1 Transcription Factor/immunology,metabolism STAT3 Transcription Factor/immunology,metabolism Signal Transduction Toll-Like Receptors/immunology,metabolism
Chemicals
STAT1 Transcription Factor STAT3 Transcription Factor Toll-Like Receptors Interleukin-10 Interferons
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hu Xiaoyu
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY, USA.
Chakravarty Soumya D
Ivashkiv Lionel B
References (113)
113 references, click to expand
  1. Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4.
    Nature. 2006 May 11;441(7090):173-8 PMID: 16688168
  2. The cell biology of macrophage activation.
    Annu Rev Immunol. 1984;2:283-318 PMID: 6100475
  3. Effect of pro-inflammatory/anti-inflammatory agents on cytokine secretion by peripheral blood mononuclear cells in rheumatoid arthritis and systemic lupus erythematosus.
    Autoimmunity. 2003 Mar;36(2):71-7 PMID: 12820688
  4. Gene-specific control of inflammation by TLR-induced chromatin modifications.
    Nature. 2007 Jun 21;447(7147):972-8 PMID: 17538624
  5. Alternative activation of STAT1 and STAT3 in response to interferon-gamma.
    J Biol Chem. 2004 Oct 1;279(40):41679-85 PMID: 15284232
  6. Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice.
    J Immunol. 1997 Jun 1;158(11):5507-13 PMID: 9164974
  7. Role of interleukin-10 in regulation of T-cell-dependent and T-cell-independent mechanisms of resistance to Toxoplasma gondii.
    Infect Immun. 1997 May;65(5):1675-82 PMID: 9125546
  8. A role for IFN-alpha beta in virus infection-induced sensitization to endotoxin.
    J Immunol. 2001 Feb 15;166(4):2658-64 PMID: 11160329
  9. How cells respond to interferons.
    Annu Rev Biochem. 1998;67:227-64 PMID: 9759489
  10. Genetic ablation of interferon-gamma up-regulates interleukin-1beta expression and enables the elicitation of collagen-induced arthritis in a nonsusceptible mouse strain.
    Arthritis Rheum. 2001 Oct;44(10):2413-24 PMID: 11665984
  11. Proinflammatory effects of IL-10 during human endotoxemia.
    J Immunol. 2000 Sep 1;165(5):2783-9 PMID: 10946310
  12. Class II cytokine receptors and their ligands: key antiviral and inflammatory modulators.
    Nat Rev Immunol. 2003 Aug;3(8):667-76 PMID: 12974481
  13. IFN consensus sequence binding protein potentiates STAT1-dependent activation of IFNgamma-responsive promoters in macrophages.
    Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):91-6 PMID: 10618376
  14. A linear signal transduction pathway involving phosphatidylinositol 3-kinase, protein kinase Cepsilon, and MAPK in mesangial cells regulates interferon-gamma-induced STAT1alpha transcriptional activation.
    J Biol Chem. 2004 Jun 25;279(26):27399-409 PMID: 15082710
  15. Ligand-induced autoregulation of IFN-gamma receptor beta chain expression in T helper cell subsets.
    Science. 1995 Nov 17;270(5239):1215-8 PMID: 7502050
  16. High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors.
    J Immunol. 1997 Jun 1;158(11):5501-6 PMID: 9164973
  17. Interferons alpha and beta as immune regulators--a new look.
    Immunity. 2001 Jun;14(6):661-4 PMID: 11420036
  18. Interferon production in patients with systemic lupus erythematosus.
    Arthritis Rheum. 1982 Jul;25(7):802-3 PMID: 6179523
  19. Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response.
    Genes Dev. 2006 Feb 1;20(3):282-96 PMID: 16452502
  20. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease.
    Cell. 1996 Feb 9;84(3):443-50 PMID: 8608598
  21. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2610-5 PMID: 12604793
  22. IL-27 activates human monocytes via STAT1 and suppresses IL-10 production but the inflammatory functions of IL-27 are abrogated by TLRs and p38.
    J Immunol. 2008 May 1;180(9):6325-33 PMID: 18424756
  23. Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection.
    Science. 2002 Sep 20;297(5589):2063-6 PMID: 12242445
  24. Development, cytokine profile and function of human interleukin 17-producing helper T cells.
    Nat Immunol. 2007 Sep;8(9):950-7 PMID: 17676044
  25. Protein ISGylation modulates the JAK-STAT signaling pathway.
    Genes Dev. 2003 Feb 15;17(4):455-60 PMID: 12600939
  26. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells.
    J Immunol. 2004 Apr 15;172(8):4733-43 PMID: 15067049
  27. Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice.
    J Exp Med. 2003 Mar 17;197(6):777-88 PMID: 12642605
  28. Type I interferon and autoimmune disease.
    Autoimmunity. 2003 Dec;36(8):445-6 PMID: 14984020
  29. High-dose cellular IL-10 exacerbates rejection and reverses effects of cyclosporine and tacrolimus in Mouse cardiac transplantation.
    Transplant Proc. 1997 Feb-Mar;29(1-2):1081-2 PMID: 9123209
  30. Does activation of the innate immune system contribute to the development of rheumatoid arthritis?
    Arthritis Rheum. 2003 Mar;48(3):590-3 PMID: 12632408
  31. Type I interferon modulation of cellular responses to cytokines and infectious pathogens: potential role in SLE pathogenesis.
    Autoimmunity. 2003 Dec;36(8):473-9 PMID: 14984024
  32. Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration.
    J Immunol. 1997 Apr 15;158(8):3971-7 PMID: 9103468
  33. Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues.
    Arthritis Rheum. 2003 Aug;48(8):2132-45 PMID: 12905466
  34. Interleukin-10 administration decreases survival in murine recipients of major histocompatibility complex disparate donor bone marrow grafts.
    Blood. 1995 Feb 1;85(3):842-51 PMID: 7833486
  35. The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2 paradigm in autoimmunity.
    Arthritis Res. 2001;3(3):136-41 PMID: 11299053
  36. IL-10 receptor dysfunction in macrophages during chronic inflammation.
    J Leukoc Biol. 2001 Oct;70(4):624-32 PMID: 11590200
  37. IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins.
    Immunity. 2006 May;24(5):563-74 PMID: 16713974
  38. Biologic basis for interleukin-1 in disease.
    Blood. 1996 Mar 15;87(6):2095-147 PMID: 8630372
  39. Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin.
    Immunity. 2008 Jul 18;29(1):68-78 PMID: 18619869
  40. IL-10 stimulates production of platelet-activating factor by monocytes of patients with active systemic lupus erythematosus (SLE).
    Clin Exp Immunol. 2000 Dec;122(3):471-6 PMID: 11122257
  41. A signal-switch hypothesis for cross-regulation of cytokine and TLR signalling pathways.
    Nat Rev Immunol. 2008 Oct;8(10):816-22 PMID: 18787561
  42. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice.
    J Clin Invest. 2008 May;118(5):1680-90 PMID: 18382764
  43. Strategies for use of IL-10 or its antagonists in human disease.
    Immunol Rev. 2008 Jun;223:114-31 PMID: 18613832
  44. p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment.
    Nat Immunol. 2002 Jan;3(1):69-75 PMID: 11743587
  45. Activation of the transcription factor ISGF3 by interferon-gamma.
    Biol Chem. 1999 Jun;380(6):699-703 PMID: 10430035
  46. Inhibition of lupus by genetic alteration of the interferon-alpha/beta receptor.
    Autoimmunity. 2003 Dec;36(8):503-10 PMID: 14984027
  47. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils.
    Immunity. 1999 Jan;10(1):39-49 PMID: 10023769
  48. Reprogramming of IL-10 activity and signaling by IFN-gamma.
    J Immunol. 2003 Nov 15;171(10):5034-41 PMID: 14607900
  49. Persistent mitochondrial hyperpolarization, increased reactive oxygen intermediate production, and cytoplasmic alkalinization characterize altered IL-10 signaling in patients with systemic lupus erythematosus.
    J Immunol. 2002 Jul 15;169(2):1092-101 PMID: 12097418
  50. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta.
    Nature. 2002 Apr 18;416(6882):744-9 PMID: 11961557
  51. Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy.
    Arthritis Rheum. 2000 Jul;43(7):1431-42 PMID: 10902743
  52. Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial.
    Arthritis Rheum. 2002 Dec;46(12):3143-50 PMID: 12483717
  53. Lack of interferon gamma receptor beta chain and the prevention of interferon gamma signaling in TH1 cells.
    Science. 1995 Jul 14;269(5221):245-7 PMID: 7618088
  54. PI3K-mediated negative feedback regulation of IL-12 production in DCs.
    Nat Immunol. 2002 Sep;3(9):875-81 PMID: 12154357
  55. Interferon-alpha: a new target for therapy in systemic lupus erythematosus?
    Arthritis Rheum. 2003 Sep;48(9):2396-401 PMID: 13130457
  56. A weak signal for strong responses: interferon-alpha/beta revisited.
    Nat Rev Mol Cell Biol. 2001 May;2(5):378-86 PMID: 11331912
  57. The emerging role of interferon in human systemic lupus erythematosus.
    Curr Opin Immunol. 2004 Dec;16(6):801-7 PMID: 15511676
  58. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation.
    J Leukoc Biol. 2007 Aug;82(2):237-43 PMID: 17502339
  59. Cytokine expression and cell activation in inflammatory arthritis.
    Adv Immunol. 1996;63:337-76 PMID: 8787634
  60. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway.
    Cell. 1996 Feb 9;84(3):431-42 PMID: 8608597
  61. Bone resorption by osteoclasts.
    Science. 2000 Sep 1;289(5484):1504-8 PMID: 10968780
  62. Interferon-gamma: an overview of signals, mechanisms and functions.
    J Leukoc Biol. 2004 Feb;75(2):163-89 PMID: 14525967
  63. PI3K and negative regulation of TLR signaling.
    Trends Immunol. 2003 Jul;24(7):358-63 PMID: 12860525
  64. IFN-alpha priming results in a gain of proinflammatory function by IL-10: implications for systemic lupus erythematosus pathogenesis.
    J Immunol. 2004 May 15;172(10):6476-81 PMID: 15128840
  65. Interleukin-10 and the interleukin-10 receptor.
    Annu Rev Immunol. 2001;19:683-765 PMID: 11244051
  66. IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis.
    J Immunol. 1996 Oct 15;157(8):3223-7 PMID: 8871615
  67. IL-6 signal transduction and its physiological roles: the signal orchestration model.
    Rev Physiol Biochem Pharmacol. 2003;149:1-38 PMID: 12687404
  68. Toll-like receptors control activation of adaptive immune responses.
    Nat Immunol. 2001 Oct;2(10):947-50 PMID: 11547333
  69. Interferon-gamma confers resistance to experimental allergic encephalomyelitis.
    Eur J Immunol. 1996 Jul;26(7):1641-6 PMID: 8766573
  70. Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma.
    J Immunol. 2004 Mar 1;172(5):2739-43 PMID: 14978071
  71. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma.
    Nature. 2000 Nov 30;408(6812):600-5 PMID: 11117749
  72. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.
    J Immunol. 1995 Aug 1;155(3):1079-90 PMID: 7543512
  73. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?
    Annu Rev Immunol. 2001;19:163-96 PMID: 11244034
  74. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus.
    Science. 2001 Nov 16;294(5546):1540-3 PMID: 11711679
  75. Comparison of the suppressive effects of interleukin-10 and interleukin-4 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis.
    Immunology. 1995 Apr;84(4):536-42 PMID: 7790026
  76. Injury primes the innate immune system for enhanced Toll-like receptor reactivity.
    J Immunol. 2003 Aug 1;171(3):1473-83 PMID: 12874240
  77. Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo.
    J Immunol. 2001 Nov 1;167(9):5067-76 PMID: 11673516
  78. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17.
    Nat Immunol. 2007 Jun;8(6):630-8 PMID: 17450144
  79. Modulation of Toll-interleukin 1 receptor mediated signaling.
    J Mol Med (Berl). 2005 Apr;83(4):258-66 PMID: 15662540
  80. The role of STAT1 in viral sensitization to LPS.
    J Endotoxin Res. 2003;9(5):313-6 PMID: 14577848
  81. Interleukin-10 receptor signaling through the JAK-STAT pathway. Requirement for two distinct receptor-derived signals for anti-inflammatory action.
    J Biol Chem. 1999 Jun 4;274(23):16513-21 PMID: 10347215
  82. The JAK/STAT pathway in rheumatoid arthritis: pathogenic or protective?
    Arthritis Rheum. 2003 Aug;48(8):2092-6 PMID: 12905460
  83. IFN-alpha skews monocyte differentiation into Toll-like receptor 7-expressing dendritic cells with potent functional activities.
    J Immunol. 2003 Oct 1;171(7):3385-93 PMID: 14500632
  84. Negative regulation of toll-like receptor-mediated immune responses.
    Nat Rev Immunol. 2005 Jun;5(6):446-58 PMID: 15928677
  85. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells.
    Nat Immunol. 2007 Sep;8(9):942-9 PMID: 17676045
  86. How important are T cells in chronic rheumatoid synovitis?: II. T cell-independent mechanisms from beginning to end.
    Arthritis Rheum. 2002 Feb;46(2):298-308 PMID: 11840432
  87. 'Tuning' of type I interferon-induced Jak-STAT1 signaling by calcium-dependent kinases in macrophages.
    Nat Immunol. 2008 Feb;9(2):186-93 PMID: 18084294
  88. Macrophages and their products in rheumatoid arthritis.
    Curr Opin Rheumatol. 2007 May;19(3):289-95 PMID: 17414958
  89. Recognition of microorganisms and activation of the immune response.
    Nature. 2007 Oct 18;449(7164):819-26 PMID: 17943118
  90. Stat3 recruitment by two distinct ligand-induced, tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain.
    J Biol Chem. 1996 Nov 1;271(44):27954-61 PMID: 8910398
  91. Dysregulation of interleukin-10-dependent gene expression in rheumatoid arthritis synovial macrophages.
    Arthritis Rheum. 2006 Sep;54(9):2711-21 PMID: 16947381
  92. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-alpha beta.
    J Immunol. 2001 Jan 15;166(2):982-8 PMID: 11145676
  93. Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase.
    J Exp Med. 2001 Oct 15;194(8):1123-40 PMID: 11602641
  94. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos.
    J Immunol. 2003 Nov 15;171(10):4984-9 PMID: 14607893
  95. Sensitization of IFN-gamma Jak-STAT signaling during macrophage activation.
    Nat Immunol. 2002 Sep;3(9):859-66 PMID: 12172544
  96. Role of cytokines in rheumatoid arthritis.
    Annu Rev Immunol. 1996;14:397-440 PMID: 8717520
  97. Cross talk between interferon-gamma and -alpha/beta signaling components in caveolar membrane domains.
    Science. 2000 Jun 30;288(5475):2357-60 PMID: 10875919
  98. T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection.
    J Immunol. 1997 Jan 1;158(1):315-21 PMID: 8977205
  99. Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS.
    J Clin Invest. 2002 Nov;110(10):1503-13 PMID: 12438448
  100. Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation.
    Genes Dev. 2003 Aug 15;17(16):1979-91 PMID: 12923053
  101. Monocyte response to Th1 stimulation and effector function toward human mesangial cells are not impaired in patients with lupus nephritis.
    Clin Immunol. 2003 Jan;106(1):65-72 PMID: 12584053
  102. Amplification of IFN-alpha-induced STAT1 activation and inflammatory function by Syk and ITAM-containing adaptors.
    Nat Immunol. 2004 Nov;5(11):1181-9 PMID: 15467722
  103. Activation and regulation of Toll-like receptors 2 and 1 in human leprosy.
    Nat Med. 2003 May;9(5):525-32 PMID: 12692544
  104. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3.
    Nat Immunol. 2005 Aug;6(8):777-84 PMID: 16007092
  105. Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies.
    Lupus. 2000;9(9):664-71 PMID: 11199920
  106. Homeostatic role of interferons conferred by inhibition of IL-1-mediated inflammation and tissue destruction.
    J Immunol. 2005 Jul 1;175(1):131-8 PMID: 15972639
  107. Local activation of STAT-1 and STAT-3 in the inflamed synovium during zymosan-induced arthritis: exacerbation of joint inflammation in STAT-1 gene-knockout mice.
    Arthritis Rheum. 2004 Jun;50(6):2014-23 PMID: 15188379
  108. Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon.
    Science. 1982 Apr 23;216(4544):429-31 PMID: 6176024
  109. Interleukin-10 response abnormalities in systemic lupus erythematosus.
    Scand J Immunol. 1997 Oct;46(4):406-12 PMID: 9350293
  110. TLR signaling.
    Semin Immunol. 2007 Feb;19(1):24-32 PMID: 17275323
  111. Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis.
    J Exp Med. 2003 Jun 2;197(11):1573-83 PMID: 12782719
  112. Lipopolysaccharide-induced expression of matrix metalloproteinases in human monocytes is suppressed by IFN-gamma via superinduction of ATF-3 and suppression of AP-1.
    J Immunol. 2008 Oct 1;181(7):5089-97 PMID: 18802113
  113. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood.
    J Exp Med. 2003 Mar 17;197(6):711-23 PMID: 12642603
Article Info
Journal
Immunological reviews
Abbr.
Immunol Rev
ISSN
1600-065X
DOI
10.1111/j.1600-065X.2008.00707.x
Published
2008-12-00
Pages
41-56
Language
English
Region
England
NLM ID
7702118
PMCID
PMC2630590
Subset
IM
Grants
NIAID NIH HHS · R01 AI046712 · United States
NIAID NIH HHS · R01 AI044938-09 · United States
NIAID NIH HHS · R01 AI046712-09 · United States
NIAID NIH HHS · R01 AI044938 · United States
NIAMS NIH HHS · R01 AR046713 · United States
NIAMS NIH HHS · R01 AR046713-10 · United States
NIAID NIH HHS · R01 AI059636-03 · United States
NIAID NIH HHS · R01 AI059636 · United States
NIAMS NIH HHS · R01 AR050401 · United States
NIAMS NIH HHS · R01 AR050401-05 · United States
External Links
PubMed source DOI: 10.1111/j.1600-065X.2008.00707.x PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2