Document Detail

Deciphering signaling outcomes from a system of complex networks.
MedLine Citation:
PMID:  19454649     Owner:  NLM     Status:  MEDLINE    
Cellular signal transduction machinery integrates information from multiple inputs to actuate discrete cellular behaviors. Interaction complexity exists when an input modulates the output behavior that results from other inputs. To address whether this machinery is iteratively complex--that is, whether increasing numbers of inputs produce exponential increases in discrete cellular behaviors--we examined the modulated secretion of six cytokines from macrophages in response to up to five-way combinations of an agonist of Toll-like receptor 4, three cytokines, and conditions that activated the cyclic adenosine monophosphate pathway. Although all of the selected ligands showed synergy in paired combinations, few examples of nonadditive outputs were found in response to higher-order combinations. This suggests that most potential interactions are not realized and that unique cellular responses are limited to discrete subsets of ligands and pathways that enhance specific cellular functions.
Robert C Hsueh; Madhusudan Natarajan; Iain Fraser; Blake Pond; Jamie Liu; Susanne Mumby; Heping Han; Lily I Jiang; Melvin I Simon; Ronald Taussig; Paul C Sternweis
Related Documents :
22567049 - Cytokine gene polymorphisms support diagnostic monitoring of romanian multiple myeloma ...
24992029 - Molecular cloning, expression and characterization of pekin duck interferon-λ
21099249 - Slit improves cedar pollinosis by restoring il-10 production from tr1 and monocytes∼i...
23566959 - P53 activation by ni(ii) is a hif-1α independent response causing caspases 9/3-mediate...
24662979 - Chemokine cxcl8 promotes hiv-1 replication in human monocyte-derived macrophages and pr...
23320049 - Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and ...
8289459 - A unified model of immune response. ii: continuum approach.
3030669 - Effects of lincomycin on the immune system.
19427399 - Mitochondrial factors in the regulation of innate immunity.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-19
Journal Detail:
Title:  Science signaling     Volume:  2     ISSN:  1937-9145     ISO Abbreviation:  Sci Signal     Publication Date:  2009  
Date Detail:
Created Date:  2009-05-20     Completed Date:  2009-10-27     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  101465400     Medline TA:  Sci Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  ra22     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Cell Line
Chemokine CCL3 / metabolism,  secretion
Chemokine CCL5 / metabolism,  secretion
Cytokines / metabolism*,  secretion
Granulocyte Colony-Stimulating Factor / genetics,  metabolism,  secretion
Interferon-beta / pharmacology
Interleukin-10 / metabolism,  secretion
Interleukin-6 / metabolism,  pharmacology,  secretion
Isoproterenol / pharmacology
Macrophages / cytology,  drug effects,  metabolism*
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects,  physiology*
Sugar Acids / pharmacology
Time Factors
Transforming Growth Factor beta / pharmacology
Tumor Necrosis Factor-alpha / metabolism,  secretion
Grant Support
GM 62114/GM/NIGMS NIH HHS; U54 GM062114/GM/NIGMS NIH HHS; U54 GM062114-089002/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Chemokine CCL3; 0/Chemokine CCL5; 0/Cytokines; 0/Interleukin-6; 0/RNA, Messenger; 0/Sugar Acids; 0/Transforming Growth Factor beta; 0/Tumor Necrosis Factor-alpha; 1069-03-0/2-keto-3-deoxyoctonate; 130068-27-8/Interleukin-10; 143011-72-7/Granulocyte Colony-Stimulating Factor; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 77238-31-4/Interferon-beta; L628TT009W/Isoproterenol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Limb development takes a measured step toward systems analysis.
Next Document:  TRPM2 functions as a lysosomal Ca2+-release channel in beta cells.