Soni2018 - IL6 induced M2 Phenotype in Leishmania major infected macrophage

  public model
Model Identifier
BIOMD0000000873
Short description

IL-6 has been proposed to favor the development of Th2 responses and play an important role in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation, differentiation and act as key player during inflammation and immune response. Th2 cytokines play an immunoregulatory role in early infection. Literature says in mice infected with L. major, IL-6 may promote the development of both Th1 and Th2 responses. IL-4 is also considered to be the signature cytokine of Th-2 response. IL6 was initially characterized as a Th1 cytokine but later on it was proved to be a pleiotropic cytokine, secreted from different cell types including the macrophages. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches may be used to tackle this challenge in an iterative process of quantitative mathematical analysis. In this study, we created an in silico model of IL6 mediated macrophage activation which suffers from an excessive impact of the negative feedback loop involving SOCS1. The strategy adopted in this framework may help to reduce the complexity of the leishmanial IL6 model analysis and also laydown various physiological or pathological conditions of IL6 signaling in future.
Format
SBML (L2V4)
Related Publication
  • Systems cues governing IL6 signaling in leishmaniasis.
  • Soni B, Saha B, Singh S
  • Cytokine , 6/ 2018 , Volume 106 , pages: 169-175 , PubMed ID: 29128405
  • National Centre for Cell Science, NCCS Complex, Ganeshkhind, SPPU Pune University Campus, Pune 411007, India.
  • IL-6 has been proposed to favor the development of Th2 responses and play an important role in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation, differentiation and act as key player during inflammation and immune response. Th2 cytokines play an immunoregulatory role in early infection. Literature says in mice infected with L. major, IL-6 may promote the development of both Th1 and Th2 responses. IL-4 is also considered to be the signature cytokine of Th-2 response. IL-10 was initially characterized as a Th2 cytokine but later on it was proved to be a pleiotropic cytokine, secreted from different cell types including the macrophages. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches may be used to tackle this challenge in an iterative process of quantitative mathematical analysis. In this study, we created an in silico model of IL6 mediated macrophage activation which suffers from an excessive impact of the negative feedback loop involving SOCS3. The strategy adopted in this framework may help to reduce the complexity of the leishmanial IL6 model analysis and also laydown various physiological or pathological conditions of IL6 signaling in future.
Contributors
Submitter of the first revision: Bhavnita Soni
Submitter of this revision: Mohammad Umer Sharif Shohan
Modellers: Krishna Kumar Tiwari, Bhavnita Soni, Mohammad Umer Sharif Shohan

Metadata information

hasInstance (1 statement)
Taxonomy Leishmania

isDescribedBy (1 statement)
Taxonomy Leishmania

Curation status
Curated
Tags

Connected external resources

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Name Description Size Actions

Model files
Soni2018.xml SBML L2V4 representation of Mathematical model of IL6 induced signaling in Leishmania major infected macrophage 159.14 KB Preview | Download

Additional files
M2 Phenotype.xml old xml file 106.27 KB Preview | Download
Soni2018.cps COPASI version 4.24 (Build 197) representation of Mathematical model of IL6 induced signaling in Leishmania major infected macrophage 213.16 KB Preview | Download
Soni2018.sedml SEDML L1V2 representation of Mathematical model of IL6 induced signaling in Leishmania major infected macrophage 22.13 KB Preview | Download

  • Model originally submitted by : Bhavnita Soni
  • Submitted: May 24, 2019 12:39:55 PM
  • Last Modified: Nov 22, 2019 4:26:33 PM
Revisions
  • Version: 6 public model Download this version
    • Submitted on: Nov 22, 2019 4:26:33 PM
    • Submitted by: Mohammad Umer Sharif Shohan
    • With comment: Automatically added model identifier BIOMD0000000873
  • Version: 4 public model Download this version
    • Submitted on: May 24, 2019 12:39:55 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
mwf219928e abba 4c09 9597 5d6910f7e4d9

Interleukin-6 receptor subunit alpha 		1000.0 mol
mwacd53f34 4935 4b6a 8267 024f0d966c8c

O64645 		10000.0 mol
mwba110304 bd9a 4fd0 9b4c b8bfc975e30b

O64645 		200.0 mol
mwfaacd7f7 6aa9 4e6c a7d8 281f2022ba2f

Toll-like receptor 2 		1000.0 mol
mw7938fab7 d0c6 497b 8fb6 75922fcc19d5

O64645 		300.0 mol
mwd5f166e6 df0a 45bf b662 e87b91b79a27

5416611 		0.0 mol
mwc84af692 e3fc 4ede 99b6 b0cce3729bf7

Signal transducer and activator of transcription 1-alpha/beta 		80000.0 mol
mwbe46ba92 97de 4cc4 970d 2dec54671573

Signal transducer and activator of transcription 1-alpha/beta 		0.0 mol
mw4fd8b902 e2a2 4910 899c 2a7d3425e0e0

Interleukin-1 receptor-associated kinase 1 		700.0 mol
Reactions
Reactions Rate Parameters
mwf219928e_abba_4c09_9597_5d6910f7e4d9 => mw57b4236e_c789_4799_a4f9_a03437a5593a mwd01d5494_fdcd_494e_8652_87201fa5b291*mwf219928e_abba_4c09_9597_5d6910f7e4d9*mw664a2e7f_0c35_423c_ac5d_34090e629a69 mwd01d5494_fdcd_494e_8652_87201fa5b291=0.002
mw3d58864c_79c7_4ff2_98fe_1a85b2ccc43d => mwacd53f34_4935_4b6a_8267_024f0d966c8c mw5805aaa6_5a0a_495b_a21b_16e6ba6f39bc*mw3d58864c_79c7_4ff2_98fe_1a85b2ccc43d*mwdfcbcdb1_3058_4a8b_9166_5b5e144c52c9 mw5805aaa6_5a0a_495b_a21b_16e6ba6f39bc=0.3
mwacd53f34_4935_4b6a_8267_024f0d966c8c + mw57b4236e_c789_4799_a4f9_a03437a5593a => mw57b4236e_c789_4799_a4f9_a03437a5593a + mwacd53f34_4935_4b6a_8267_024f0d966c8c mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22*mw658feef9_67a1_431f_95fa_7358c6b294d2*mw57b4236e_c789_4799_a4f9_a03437a5593a*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22/(mw8d03d46b_3832_4fe6_8a6b_467ef38af206*(1+mwacd53f34_4935_4b6a_8267_024f0d966c8c*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22/mwf50b6519_aaf9_4cb0_a651_d5a3159d7390)+mw57b4236e_c789_4799_a4f9_a03437a5593a*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22)/mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22 mw8d03d46b_3832_4fe6_8a6b_467ef38af206=10.0; mw658feef9_67a1_431f_95fa_7358c6b294d2=1.0E-15; mwf50b6519_aaf9_4cb0_a651_d5a3159d7390=10.0
mw7938fab7_d0c6_497b_8fb6_75922fcc19d5 => mwba110304_bd9a_4fd0_9b4c_b8bfc975e30b mwe0f7b31e_2efc_481e_90d0_e86c3b8d0be4*mw7938fab7_d0c6_497b_8fb6_75922fcc19d5*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22 mwe0f7b31e_2efc_481e_90d0_e86c3b8d0be4=0.125
mwfaacd7f7_6aa9_4e6c_a7d8_281f2022ba2f + mwa244ea2a_3e41_473b_9ae7_d0db512fc366 + mw763cffc8_c121_4004_afdb_97e9de9f0081 => mw6339814d_af4c_4eee_9455_7e20795f6aeb mw664a2e7f_0c35_423c_ac5d_34090e629a69*mwf80a94ba_03ba_44f0_b793_4f60c20fd074*mwfaacd7f7_6aa9_4e6c_a7d8_281f2022ba2f*mw664a2e7f_0c35_423c_ac5d_34090e629a69*mwa244ea2a_3e41_473b_9ae7_d0db512fc366*mw664a2e7f_0c35_423c_ac5d_34090e629a69*mw763cffc8_c121_4004_afdb_97e9de9f0081*mw664a2e7f_0c35_423c_ac5d_34090e629a69/mw664a2e7f_0c35_423c_ac5d_34090e629a69 mwf80a94ba_03ba_44f0_b793_4f60c20fd074=8.0E-9
mw78198c86_4b16_4117_8592_6a95c3953126 => mw7938fab7_d0c6_497b_8fb6_75922fcc19d5 mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22*mwb8d480f9_5783_4feb_aaf1_2f861b09e009*mw78198c86_4b16_4117_8592_6a95c3953126*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22/mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22 mwb8d480f9_5783_4feb_aaf1_2f861b09e009=0.14
mw57b4236e_c789_4799_a4f9_a03437a5593a + mwb9a40fab_a7c9_4984_805f_045fefc4ff32 => mwd5f166e6_df0a_45bf_b662_e87b91b79a27 mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22*mw7ff2e94a_ac19_47ed_9127_14d385a1e544*mwb9a40fab_a7c9_4984_805f_045fefc4ff32*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22/(mwf8062aeb_69d6_416b_b877_9687ef6fbc80+mwb9a40fab_a7c9_4984_805f_045fefc4ff32*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22)/mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22 mwf8062aeb_69d6_416b_b877_9687ef6fbc80=1.0; mw7ff2e94a_ac19_47ed_9127_14d385a1e544=1.0
mwc84af692_e3fc_4ede_99b6_b0cce3729bf7 => mw55b6f083_2b28_4a1a_ab90_82a751525d72 mwf5ba0e23_9a0b_4bf6_b0ea_9fbc91843b5c*mwc84af692_e3fc_4ede_99b6_b0cce3729bf7*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22 mwf5ba0e23_9a0b_4bf6_b0ea_9fbc91843b5c=0.1
mwbe46ba92_97de_4cc4_970d_2dec54671573 => mw3d58864c_79c7_4ff2_98fe_1a85b2ccc43d mwdfcbcdb1_3058_4a8b_9166_5b5e144c52c9*mw051e0a03_1d45_448b_be4a_9d489e1b3ff9*(mwbe46ba92_97de_4cc4_970d_2dec54671573*mwdfcbcdb1_3058_4a8b_9166_5b5e144c52c9)^mwf9b630f8_c8a5_4fd0_bef1_92819b1257d2/(mw322ca6ab_81cf_4f6c_835e_48bb5f8b11de+(mwbe46ba92_97de_4cc4_970d_2dec54671573*mwdfcbcdb1_3058_4a8b_9166_5b5e144c52c9)^mwf9b630f8_c8a5_4fd0_bef1_92819b1257d2)/mwdfcbcdb1_3058_4a8b_9166_5b5e144c52c9 mw322ca6ab_81cf_4f6c_835e_48bb5f8b11de=0.0; mw051e0a03_1d45_448b_be4a_9d489e1b3ff9=0.0; mwf9b630f8_c8a5_4fd0_bef1_92819b1257d2=0.0
mw4fd8b902_e2a2_4910_899c_2a7d3425e0e0 => mwf06c0537_577b_4f13_a9a3_521f9d2217fb mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22*mw5b78650d_d92f_4602_bbe9_66d900ff312e*mw4fd8b902_e2a2_4910_899c_2a7d3425e0e0*mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22/mwfef402b9_4b7e_4fbd_bba2_ff8998ab0b22 mw5b78650d_d92f_4602_bbe9_66d900ff312e=0.22
Curator's comment:
(added: 22 Nov 2019, 16:26:24, updated: 22 Nov 2019, 16:26:24)
The model has been encoded in COPASI 4.24 (Build 197) and the Figure 3B has been generated using COPASI 4.24 (Build 197) Although some of the contents are missing but the figure is exact for the contents shown in the figure